Inconsistent output between LOVD and VV endpoints as well as hg19 and hg38 input.

[ifokkema]

Describe the bug
Not sure if related to #202.

Variant NC_000008.10:g.6673379del (hg19/GRCh37) provides very strange mappings when using the VV endpoint, but not when using the LOVD endpoint. There is a gap warning, but somehow both endpoints deal with this differently.

The LOVD endpoint produces results like I would expect; filtered output:

{
  "NC_000008.10:g.6673379del": {
    "NC_000008.10:g.6673379del": {
      "g_hgvs": "NC_000008.10:g.6673379del",
      "hgvs_t_and_p": {
        "NM_001289973.1": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_001289973.1:c.380C>T",
        },
        "NM_001289973.2": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_001289973.2:c.380C>T",
        },
        "NM_207411.4": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_207411.4:c.869C>T",
        },
        "NM_207411.5": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_207411.5:c.869C>T",
        }
      }
    }
  }
}

You can see that all mappings to transcripts are substitutions and not deletions (likely the result of the misalignment), but the mappings back to the genome are deletions again. So, what I put in, I also get out.

However, VV does something else entirely. Again, filtered output:

{
  "NM_001289973.1:c.380C>T": {
    "hgvs_transcript_variant": "NM_001289973.1:c.380C>T",
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000008.10:g.6673379G>A",
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
      }
    },
    "submitted_variant": "NC_000008.10:g.6673379del",
  },
  "NM_001289973.2:c.380C>T": {
    "hgvs_transcript_variant": "NM_001289973.2:c.380C>T",
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000008.10:g.6673379G>A",
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
      }
    },
    "submitted_variant": "NC_000008.10:g.6673379del",
  },
  "NM_207411.4:c.869C>T": {
    "hgvs_transcript_variant": "NM_207411.4:c.869C>T",
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000008.10:g.6673379G>A",
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
      }
    },
    "submitted_variant": "NC_000008.10:g.6673379del",
  },
  "NM_207411.5:c.869C>T": {
    "hgvs_transcript_variant": "NM_207411.5:c.869C>T",
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000008.10:g.6673379G>A",
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
      },
    },
    "submitted_variant": "NC_000008.10:g.6673379del",
  }
}

So, even though again the mapping to the transcripts results in substitutions, all of a sudden mapping back to the genome results in substitutions as well. So, when mapping the genomic variant to the transcript and then back, I lose my original variant description!

I thought this was maybe due to coding differences between VV and VF, but now I'm not so sure.

The LOVD endpoint again but this time with the hg38 variant displays a new issue:

{
  "NC_000008.11:g.6815857del": {
    "NC_000008.11:g.6815857del": {
      "g_hgvs": "NC_000008.11:g.6815857del",
      "hgvs_t_and_p": {
        "NM_001289973.1": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_001289973.1:c.380del",
        },
        "NM_001289973.2": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_001289973.2:c.380del",
        },
        "NM_207411.4": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_207411.4:c.869del",
        },
        "NM_207411.5": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_207411.5:c.869del",
        }
      }
    }
  }
}

Now, the mappings to the transcripts aren't substitutions anymore. There's also no gap warning.

Finally, the hg38 variant on the VV endpoint presents only deletions, and returns my input as well.

{
  "NM_001289973.1:c.380del": {
    "hgvs_transcript_variant": "NM_001289973.1:c.380del",
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000008.10:g.6673379_6673380del",
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000008.11:g.6815857del",
      }
    },
    "submitted_variant": "NC_000008.11:g.6815857del",
  },
  "NM_001289973.2:c.380del": {
    "hgvs_transcript_variant": "NM_001289973.2:c.380del",
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000008.10:g.6673379_6673380del",
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000008.11:g.6815857del",
      }
    },
    "submitted_variant": "NC_000008.11:g.6815857del",
  },
  "NM_207411.4:c.869del": {
    "hgvs_transcript_variant": "NM_207411.4:c.869del",
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000008.10:g.6673379_6673380del",
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000008.11:g.6815857del",
      }
    },
    "submitted_variant": "NC_000008.11:g.6815857del",
  },
  "NM_207411.5:c.869del": {
    "hgvs_transcript_variant": "NM_207411.5:c.869del",
    "primary_assembly_loci": {
      "grch37": {
        "hgvs_genomic_description": "NC_000008.10:g.6673379_6673380del",
      },
      "grch38": {
        "hgvs_genomic_description": "NC_000008.11:g.6815857del",
      }
    },
    "submitted_variant": "NC_000008.11:g.6815857del",
  }
}

Note that for the hg19 mappings, all of a sudden the deletions are ranges.

What could cause these inconsistencies?

• VV returns genomic mappings that do not match the input, but only when using the hg19 variant.
• When using the hg19 input, VV returns all substitutions. When using the hg38 input, VV returns all deletions, of which the hg19 mappings are deletions of two bases.
• The hg38 mapping provided by the LOVD endpoint isn't handled the same as the same variant on hg19, either, but differently from how VV handles them.

To Reproduce
See links in the above report.

Expected behavior

• No matter which endpoint I use, for one specific input, the given mappings should be the same for all endpoints.
• My genomic input should also be returned in the output as a valid mapping.
• The hg19 variant and its equivalent on hg38 should produce the same mappings.

[Peter-J-Freeman]

Gonna look at these 1 at a time.

Here is the first variant g_to_t handled by VV

import json
import VariantValidator
vval = VariantValidator.Validator()
variant = 'NC_000008.10:g.6673379del' # variant 1
genome_build = 'GRCh37' # First look at GRCh37
select_transcripts = 'mane'
transcript_set = 'refseq'
validate = vval.validate(variant, genome_build, select_transcripts, transcript_set)
validation = validate.format_as_dict(with_meta=True)
print(json.dumps(validation, sort_keys=True, indent=4, separators=(',', ': ')))

{
    "NM_207411.5:c.869C>T": {
        "alt_genomic_loci": [
            {
                "grch38": {
                    "hgvs_genomic_description": "NW_018654717.1:g.211129G>A",
                    "vcf": {
                        "alt": "A",
                        "chr": "HG76_PATCH",
                        "pos": "211129",
                        "ref": "G"
                    }
                }
            },
            {
                "hg38": {
                    "hgvs_genomic_description": "NW_018654717.1:g.211129G>A",
                    "vcf": {
                        "alt": "A",
                        "chr": "NW_018654717.1",
                        "pos": "211129",
                        "ref": "G"
                    }
                }
            }
        ],
        "annotations": {
            "chromosome": "8",
            "db_xref": {
                "CCDS": "CCDS47763.2",
                "ensemblgene": null,
                "hgnc": "HGNC:20782",
                "ncbigene": "389610",
                "select": "MANE"
            },
            "ensembl_select": false,
            "mane_plus_clinical": false,
            "mane_select": true,
            "map": "8p23.1",
            "note": "XK related 5",
            "refseq_select": true,
            "variant": "1"
        },
        "gene_ids": {
            "ccds_ids": [
                "CCDS47763"
            ],
            "ensembl_gene_id": "ENSG00000275591",
            "entrez_gene_id": "389610",
            "hgnc_id": "HGNC:20782",
            "omim_id": [],
            "ucsc_id": "uc033baq.2"
        },
        "gene_symbol": "XKR5",
        "genome_context_intronic_sequence": "",
        "hgvs_lrg_transcript_variant": "",
        "hgvs_lrg_variant": "",
        "hgvs_predicted_protein_consequence": {
            "lrg_slr": "",
            "lrg_tlr": "",
            "slr": "NP_997294.3:p.(S290L)",
            "tlr": "NP_997294.3:p.(Ser290Leu)"
        },
        "hgvs_refseqgene_variant": "",
        "hgvs_transcript_variant": "NM_207411.5:c.869C>T",
        "primary_assembly_loci": {
            "grch37": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379G>A",
                "vcf": {
                    "alt": "A",
                    "chr": "8",
                    "pos": "6673379",
                    "ref": "G"
                }
            },
            "grch38": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
                "vcf": {
                    "alt": "A",
                    "chr": "8",
                    "pos": "6815857",
                    "ref": "G"
                }
            },
            "hg19": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379G>A",
                "vcf": {
                    "alt": "A",
                    "chr": "chr8",
                    "pos": "6673379",
                    "ref": "G"
                }
            },
            "hg38": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
                "vcf": {
                    "alt": "A",
                    "chr": "chr8",
                    "pos": "6815857",
                    "ref": "G"
                }
            }
        },
        "reference_sequence_records": {
            "protein": "https://www.ncbi.nlm.nih.gov/nuccore/NP_997294.3",
            "transcript": "https://www.ncbi.nlm.nih.gov/nuccore/NM_207411.5"
        },
        "refseqgene_context_intronic_sequence": "",
        "selected_assembly": "GRCh37",
        "submitted_variant": "NC_000008.10:g.6673379del",
        "transcript_description": "Homo sapiens XK related 5 (XKR5), transcript variant 1, mRNA",
        "validation_warnings": [],
        "variant_exonic_positions": {
            "NC_000008.10": {
                "end_exon": "6",
                "start_exon": "6"
            },
            "NC_000008.11": {
                "end_exon": "6",
                "start_exon": "6"
            }
        }
    },
    "flag": "gene_variant",
    "metadata": {
        "variantvalidator_hgvs_version": "2.0.2.dev1+g6ecbf8e",
        "variantvalidator_version": "1.0.5.dev275+ge591818.d20220711",
        "vvdb_version": "vvdb_2022_04",
        "vvseqrepo_db": "VV_SR_2022_02/master",
        "vvta_version": "vvta_2022_02"
    }
}

So I agree, it looks like the VV endpoint is not getting back to the variant = 'NC_000008.10:g.6673379del but is correctly mapping from variant = 'NC_000008.10:g.6673379del to NM_207411.5:c.869C>T.

I suspect that there might still be a difference between VV and VF/LOVD which means that variants do not map back in quite the same way. I will see if I can isolate and correct this.

For this variant and GRCh37, VF/LOVD does this as stated by @ifokkema

{
  "NC_000008.10:g.6673379del": {
    "NC_000008.10:g.6673379del": {
      "g_hgvs": "NC_000008.10:g.6673379del",
      "hgvs_t_and_p": {
        "NM_001289973.1": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_001289973.1:c.380C>T",
        },
        "NM_001289973.2": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_001289973.2:c.380C>T",
        },
        "NM_207411.4": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_207411.4:c.869C>T",
        },
        "NM_207411.5": {
          "primary_assembly_loci": {
            "grch37": {
              "NC_000008.10": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del",
              }
            },
            "grch38": {
              "NC_000008.11": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
              }
            }
          },
          "t_hgvs": "NM_207411.5:c.869C>T",
        }
      }
    }
  }
}

[Peter-J-Freeman]

Here is the GRCh37 alignment

[Peter-J-Freeman]

So g.6673375del should indeed be NM_001289973.1:c.380C>T where the G/C is deleted from the genome but the A/T is present instead of the gap.

The map back however is returning NC_000008.10:g.6673379G>A which is technically correct because the base is now at an aligned position, but really ought to consider the gap as well since the 2 are adjacent. This illustrates the actual issue I think

[ifokkema]

So g.6673375del should indeed be NM_001289973.1:c.380C>T where the G/C is deleted from the genome but the A/T is present instead of the gap.

You mean NC_000008.10:g.6673379del (last digit is different), right?

The map back however is returning NC_000008.10:g.6673379G>A which is technically correct because the base is now at an aligned position, but really ought to consider the gap as well since the 2 are adjacent. This illustrates the actual issue I think

I agree; I really thought that specifying variants adjacent to a gap always includes the gap when mapping, but perhaps that was with other endpoints? Either way, I think we ran into something similar before, where we had to think about the range that we'd include. So, basically, if you claim c.100C>T, we agree that includes c.99= and c.101=, but how far do we go? If there is no verdict on SVD-WG010 yet, I believe we should keep it at that interval? (note, 5' and 3' shifting should be applied here, before determining the interval)

So then, NM_001289973.1:c.380C>T includes NM_001289973.1:c.379= and NM_001289973.1:c.381=, therefore, it maps to NC_000008.10:g.6673377_6673380CAGA>CAA, normalized to NC_000008.10:g.6673379del. That matches the input.

[Peter-J-Freeman]

Agreed to all. I think I know what might be going on. Think it's related to VV not mapping back to the correct genome coords (as shown above). Will get to it asap.

Thanks for the interpretations. Makes life easier.

[Peter-J-Freeman]

Ok, just writing this so I can see my own working.

NC_000008.10:g.6673377_6673380CAGA>CAA is equivalent to NC_000008.10:g.6673379delG

[Peter-J-Freeman]

OK, so far I have (note: working on VV at the moment, not vf/lovd)

import json
import VariantValidator
vval = VariantValidator.Validator()
variant = 'NM_001289973.1:c.380C>T'
genome_build = 'hg19'
select_transcripts = 'mane'
validate = vval.validate(variant, genome_build, select_transcripts)
validation = validate.format_as_dict(with_meta=True)
print(json.dumps(validation, sort_keys=True, indent=4, separators=(',', ': ')))

{
    "NM_001289973.1:c.380C>T": {
        "alt_genomic_loci": [],
        "annotations": {
            "chromosome": "8",
            "db_xref": {
                "CCDS": null,
                "ensemblgene": null,
                "hgnc": "HGNC:20782",
                "ncbigene": "389610",
                "select": false
            },
            "ensembl_select": false,
            "mane_plus_clinical": false,
            "mane_select": false,
            "map": "8p23.1",
            "note": "XK related 5",
            "refseq_select": false,
            "variant": "2"
        },
        "gene_ids": {
            "ccds_ids": [
                "CCDS47763"
            ],
            "ensembl_gene_id": "ENSG00000275591",
            "entrez_gene_id": "389610",
            "hgnc_id": "HGNC:20782",
            "omim_id": [],
            "ucsc_id": "uc033baq.2"
        },
        "gene_symbol": "XKR5",
        "genome_context_intronic_sequence": "",
        "hgvs_lrg_transcript_variant": "",
        "hgvs_lrg_variant": "",
        "hgvs_predicted_protein_consequence": {
            "lrg_slr": "",
            "lrg_tlr": "",
            "slr": "NP_001276902.1:p.(S127L)",
            "tlr": "NP_001276902.1:p.(Ser127Leu)"
        },
        "hgvs_refseqgene_variant": "",
        "hgvs_transcript_variant": "NM_001289973.1:c.380C>T",
        "primary_assembly_loci": {
            "grch37": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del", # ???
                "vcf": {
                    "alt": "A",
                    "chr": "8",
                    "pos": "6673378",
                    "ref": "AG"
                }
            },
            "grch38": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
                "vcf": {
                    "alt": "A",
                    "chr": "8",
                    "pos": "6815857",
                    "ref": "G"
                }
            },
            "hg19": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379del", # ???
                "vcf": {
                    "alt": "A",
                    "chr": "chr8",
                    "pos": "6673378",
                    "ref": "AG"
                }
            },
            "hg38": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
                "vcf": {
                    "alt": "A",
                    "chr": "chr8",
                    "pos": "6815857",
                    "ref": "G"
                }
            }
        },
        "reference_sequence_records": {
            "protein": "https://www.ncbi.nlm.nih.gov/nuccore/NP_001276902.1",
            "transcript": "https://www.ncbi.nlm.nih.gov/nuccore/NM_001289973.1"
        },
        "refseqgene_context_intronic_sequence": "",
        "selected_assembly": "hg19",
        "submitted_variant": "NM_001289973.1:c.380C>T",
        "transcript_description": "Homo sapiens XK related 5 (XKR5), transcript variant 2, mRNA",
        "validation_warnings": [
            "Caution should be used when reporting the displayed variant descriptions: If you are unsure, please contact admin",
            "The displayed variants may be artefacts of aligning NM_001289973.1 with genomic reference NC_000008.10",
            "A more recent version of the selected reference sequence NM_001289973.1 is available (NM_001289973.2): NM_001289973.2:c.380C>T MUST be fully validated prior to use in reports: select_variants=NM_001289973.2:c.380C>T"
        ],
        "variant_exonic_positions": {
            "NC_000008.10": {
                "end_exon": "7",
                "start_exon": "7"
            },
            "NC_000008.11": {
                "end_exon": "7",
                "start_exon": "7"
            }
        }
    },
    "flag": "gene_variant",
    "metadata": {
        "variantvalidator_hgvs_version": "2.0.2.dev1+g6ecbf8e",
        "variantvalidator_version": "1.0.5.dev275+ge591818.d20220711",
        "vvdb_version": "vvdb_2022_04",
        "vvseqrepo_db": "VV_SR_2022_02/master",
        "vvta_version": "vvta_2022_02"
    }
}

@ifokkema, correct????

[ifokkema]

Looks good at first glance! I see the transcript has no gaps with hg38/GRCh38, so indeed, the NC_000008.11 description should be a substitution.

[Peter-J-Freeman]

Might be a while. Gotta iron out the bugs the new code has created

[Peter-J-Freeman]

Actually, might not be too bad. Will try a few things and add some more tests then look to push

[Peter-J-Freeman]

OK, next check please @ifokkema

import json
import VariantValidator
vval = VariantValidator.Validator()
variant = 'NC_000008.11:g.6815857del' # variant 1
genome_build = 'GRCh37'
select_transcripts = 'mane'
transcript_set = 'refseq'
validate = vval.validate(variant, genome_build, select_transcripts, transcript_set)
validation = validate.format_as_dict(with_meta=True)
print(json.dumps(validation, sort_keys=True, indent=4, separators=(',', ': ')))

{
    "NM_207411.5:c.869del": {
        "alt_genomic_loci": [
            {
                "grch38": {
                    "hgvs_genomic_description": "NW_018654717.1:g.211129del",
                    "vcf": {
                        "alt": "C",
                        "chr": "HG76_PATCH",
                        "pos": "211128",
                        "ref": "CG"
                    }
                }
            },
            {
                "hg38": {
                    "hgvs_genomic_description": "NW_018654717.1:g.211129del",
                    "vcf": {
                        "alt": "C",
                        "chr": "NW_018654717.1",
                        "pos": "211128",
                        "ref": "CG"
                    }
                }
            }
        ],
        "annotations": {
            "chromosome": "8",
            "db_xref": {
                "CCDS": "CCDS47763.2",
                "ensemblgene": null,
                "hgnc": "HGNC:20782",
                "ncbigene": "389610",
                "select": "MANE"
            },
            "ensembl_select": false,
            "mane_plus_clinical": false,
            "mane_select": true,
            "map": "8p23.1",
            "note": "XK related 5",
            "refseq_select": true,
            "variant": "1"
        },
        "gene_ids": {
            "ccds_ids": [
                "CCDS47763"
            ],
            "ensembl_gene_id": "ENSG00000275591",
            "entrez_gene_id": "389610",
            "hgnc_id": "HGNC:20782",
            "omim_id": [],
            "ucsc_id": "uc033baq.2"
        },
        "gene_symbol": "XKR5",
        "genome_context_intronic_sequence": "",
        "hgvs_lrg_transcript_variant": "",
        "hgvs_lrg_variant": "",
        "hgvs_predicted_protein_consequence": {
            "lrg_slr": "",
            "lrg_tlr": "",
            "slr": "NP_997294.3:p.(S290Cfs*8)",
            "tlr": "NP_997294.3:p.(Ser290CysfsTer8)"
        },
        "hgvs_refseqgene_variant": "",
        "hgvs_transcript_variant": "NM_207411.5:c.869del",
        "primary_assembly_loci": {
            "grch37": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379_6673380del",
                "vcf": {
                    "alt": "C",
                    "chr": "8",
                    "pos": "6673377",
                    "ref": "CAG"
                }
            },
            "grch38": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",
                "vcf": {
                    "alt": "C",
                    "chr": "8",
                    "pos": "6815856",
                    "ref": "CG"
                }
            },
            "hg19": {
                "hgvs_genomic_description": "NC_000008.10:g.6673379_6673380del", # 2bp del because of gap
                "vcf": {
                    "alt": "C",
                    "chr": "chr8",
                    "pos": "6673377",
                    "ref": "CAG"
                }
            },
            "hg38": {
                "hgvs_genomic_description": "NC_000008.11:g.6815857del",  # 1bp del
                "vcf": {
                    "alt": "C",
                    "chr": "chr8",
                    "pos": "6815856",
                    "ref": "CG"
                }
            }
        },
        "reference_sequence_records": {
            "protein": "https://www.ncbi.nlm.nih.gov/nuccore/NP_997294.3",
            "transcript": "https://www.ncbi.nlm.nih.gov/nuccore/NM_207411.5"
        },
        "refseqgene_context_intronic_sequence": "",
        "selected_assembly": "GRCh37",
        "submitted_variant": "NC_000008.11:g.6815857del",
        "transcript_description": "Homo sapiens XK related 5 (XKR5), transcript variant 1, mRNA",
        "validation_warnings": [
            "Removing redundant reference bases from variant description",
            "Caution should be used when reporting the displayed variant descriptions: If you are unsure, please contact admin",
            "The displayed variants may be artefacts of aligning NM_207411.5 with genomic reference NC_000008.10"
        ], # Warning given
        "variant_exonic_positions": {
            "NC_000008.10": {
                "end_exon": "6",
                "start_exon": "6"
            },
            "NC_000008.11": {
                "end_exon": "6",
                "start_exon": "6"
            }
        }
    },
    "flag": "gene_variant",
    "metadata": {
        "variantvalidator_hgvs_version": "2.0.2.dev1+g6ecbf8e",
        "variantvalidator_version": "1.0.5.dev275+ge591818.d20220711",
        "vvdb_version": "vvdb_2022_04",
        "vvseqrepo_db": "VV_SR_2022_02/master",
        "vvta_version": "vvta_2022_02"
    }
}

[Peter-J-Freeman]

p.s. tests completed for VV so if this is right I can make sure VF/LOVD is working correctly. please let me know ASAP @ifokkema

[Peter-J-Freeman]

http://127.0.0.1:5000/LOVD/lovd/hg19/NC_000008.10%3Ag.6673379del/refseq/all/tx/primary?content-type=application%2Fjson

gives

{
"NC_000008.10:g.6673379del": {
"NC_000008.10:g.6673379del": {
"g_hgvs": "NC_000008.10:g.6673379del",
"genomic_variant_error": null,
"hgvs_t_and_p": {
"NM_001289973.1": {
"alt_genomic_loci": [],
"gap_statement": "Genome position NC_000008.10:g.6673380 aligns within a Requires Analysis-bp gap in transcript NM_001289973.1 between positions c.380_381",
"gapped_alignment_warning": "NC_000008.10:g.6673379delG does not represent a true variant because it is an artefact of aligning NM_001289973.1 with genome build GRCh37",
"p_hgvs_slc": null,
"p_hgvs_tlc": null,
"primary_assembly_loci": {
"grch37": {
"NC_000008.10": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6673378",
"ref": "AG"
}
}
},
"grch38": {
"NC_000008.11": {
"hgvs_genomic_description": "NC_000008.11:g.6815857del",
"vcf": {
"alt": "C",
"chr": "8",
"pos": "6815856",
"ref": "CG"
}
}
},
"hg19": {
"NC_000008.10": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6673378",
"ref": "AG"
}
}
},
"hg38": {
"NC_000008.11": {
"hgvs_genomic_description": "NC_000008.11:g.6815857del",
"vcf": {
"alt": "C",
"chr": "chr8",
"pos": "6815856",
"ref": "CG"
}
}
}
},
"t_hgvs": "NM_001289973.1:c.380C>T",
"transcript_variant_error": null
},
"NM_001289973.2": {
"alt_genomic_loci": [],
"gap_statement": "Genome position NC_000008.10:g.6673380 aligns within a Requires Analysis-bp gap in transcript NM_001289973.2 between positions c.380_381",
"gapped_alignment_warning": "NC_000008.10:g.6673379delG does not represent a true variant because it is an artefact of aligning NM_001289973.2 with genome build GRCh37",
"p_hgvs_slc": null,
"p_hgvs_tlc": null,
"primary_assembly_loci": {
"grch37": {
"NC_000008.10": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6673378",
"ref": "AG"
}
}
},
"grch38": {
"NC_000008.11": {
"hgvs_genomic_description": "NC_000008.11:g.6815857del",
"vcf": {
"alt": "C",
"chr": "8",
"pos": "6815856",
"ref": "CG"
}
}
},
"hg19": {
"NC_000008.10": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6673378",
"ref": "AG"
}
}
},
"hg38": {
"NC_000008.11": {
"hgvs_genomic_description": "NC_000008.11:g.6815857del",
"vcf": {
"alt": "C",
"chr": "chr8",
"pos": "6815856",
"ref": "CG"
}
}
}
},
"t_hgvs": "NM_001289973.2:c.380C>T",
"transcript_variant_error": null
},
"NM_207411.4": {
"alt_genomic_loci": [],
"gap_statement": "Genome position NC_000008.10:g.6673380 aligns within a Requires Analysis-bp gap in transcript NM_207411.4 between positions c.869_870",
"gapped_alignment_warning": "NC_000008.10:g.6673379delG does not represent a true variant because it is an artefact of aligning NM_207411.4 with genome build GRCh37",
"p_hgvs_slc": null,
"p_hgvs_tlc": null,
"primary_assembly_loci": {
"grch37": {
"NC_000008.10": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6673378",
"ref": "AG"
}
}
},
"grch38": {
"NC_000008.11": {
"hgvs_genomic_description": "NC_000008.11:g.6815857del",
"vcf": {
"alt": "C",
"chr": "8",
"pos": "6815856",
"ref": "CG"
}
}
},
"hg19": {
"NC_000008.10": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6673378",
"ref": "AG"
}
}
},
"hg38": {
"NC_000008.11": {
"hgvs_genomic_description": "NC_000008.11:g.6815857del",
"vcf": {
"alt": "C",
"chr": "chr8",
"pos": "6815856",
"ref": "CG"
}
}
}
},
"t_hgvs": "NM_207411.4:c.869C>T",
"transcript_variant_error": null
},
"NM_207411.5": {
"alt_genomic_loci": [],
"gap_statement": "Genome position NC_000008.10:g.6673380 aligns within a Requires Analysis-bp gap in transcript NM_207411.5 between positions c.869_870",
"gapped_alignment_warning": "NC_000008.10:g.6673379delG does not represent a true variant because it is an artefact of aligning NM_207411.5 with genome build GRCh37",
"p_hgvs_slc": null,
"p_hgvs_tlc": null,
"primary_assembly_loci": {
"grch37": {
"NC_000008.10": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6673378",
"ref": "AG"
}
}
},
"grch38": {
"NC_000008.11": {
"hgvs_genomic_description": "NC_000008.11:g.6815857del",
"vcf": {
"alt": "C",
"chr": "8",
"pos": "6815856",
"ref": "CG"
}
}
},
"hg19": {
"NC_000008.10": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6673378",
"ref": "AG"
}
}
},
"hg38": {
"NC_000008.11": {
"hgvs_genomic_description": "NC_000008.11:g.6815857del",
"vcf": {
"alt": "C",
"chr": "chr8",
"pos": "6815856",
"ref": "CG"
}
}
}
},
"t_hgvs": "NM_207411.5:c.869C>T",
"transcript_variant_error": null
}
},
"p_vcf": "8:6673378:AG:A",
"selected_build": "hg19"
},
"errors": [],
"flag": null
},
"metadata": {
"variantformatter_version": "1.0.2.dev34+g3796474.d20220624",
"variantvalidator_hgvs_version": "2.0.2.dev1+g6ecbf8e",
"variantvalidator_version": "1.0.5.dev275+ge591818.d20220711",
"vvdb_version": "vvdb_2022_04",
"vvseqrepo_db": "VV_SR_2022_02/master",
"vvta_version": "vvta_2022_02"
}
}

consistent with what @ifokkema states at the top

[Peter-J-Freeman]

VV now gives

http://127.0.0.1:5000/VariantValidator/variantvalidator/hg19/NC_000008.10%3Ag.6673379del/all?content-type=application%2Fjson

{
"NM_001289973.1:c.380C>T": {
"alt_genomic_loci": [],
"annotations": {
"chromosome": "8",
"db_xref": {
"CCDS": null,
"ensemblgene": null,
"hgnc": "HGNC:20782",
"ncbigene": "389610",
"select": false
},
"ensembl_select": false,
"mane_plus_clinical": false,
"mane_select": false,
"map": "8p23.1",
"note": "XK related 5",
"refseq_select": false,
"variant": "2"
},
"gene_ids": {
"ccds_ids": [
"CCDS47763"
],
"ensembl_gene_id": "ENSG00000275591",
"entrez_gene_id": "389610",
"hgnc_id": "HGNC:20782",
"omim_id": [],
"ucsc_id": "uc033baq.2"
},
"gene_symbol": "XKR5",
"genome_context_intronic_sequence": "",
"hgvs_lrg_transcript_variant": "",
"hgvs_lrg_variant": "",
"hgvs_predicted_protein_consequence": {
"lrg_slr": "",
"lrg_tlr": "",
"slr": "NP_001276902.1:p.(S127L)",
"tlr": "NP_001276902.1:p.(Ser127Leu)"
},
"hgvs_refseqgene_variant": "",
"hgvs_transcript_variant": "NM_001289973.1:c.380C>T",
"primary_assembly_loci": {
"grch37": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6673378",
"ref": "AG"
}
},
"grch38": {
"hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6815857",
"ref": "G"
}
},
"hg19": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6673378",
"ref": "AG"
}
},
"hg38": {
"hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6815857",
"ref": "G"
}
}
},
"reference_sequence_records": {
"protein": "https://www.ncbi.nlm.nih.gov/nuccore/NP_001276902.1",
"transcript": "https://www.ncbi.nlm.nih.gov/nuccore/NM_001289973.1"
},
"refseqgene_context_intronic_sequence": "",
"selected_assembly": "hg19",
"submitted_variant": "NC_000008.10:g.6673379del",
"transcript_description": "Homo sapiens XK related 5 (XKR5), transcript variant 2, mRNA",
"validation_warnings": [
"Caution should be used when reporting the displayed variant descriptions: If you are unsure, please contact admin",
"The displayed variants may be artefacts of aligning NM_001289973.1 with genomic reference NC_000008.10",
"A more recent version of the selected reference sequence NM_001289973.1 is available (NM_001289973.2): NM_001289973.2:c.380C>T MUST be fully validated prior to use in reports: select_variants=NM_001289973.2:c.380C>T",
"The displayed variants may be artefacts of aligning NM_001289973.2 with genomic reference NC_000008.10",
"The displayed variants may be artefacts of aligning NM_207411.4 with genomic reference NC_000008.10",
"A more recent version of the selected reference sequence NM_207411.4 is available (NM_207411.5): NM_207411.5:c.869C>T MUST be fully validated prior to use in reports: select_variants=NM_207411.5:c.869C>T",
"The displayed variants may be artefacts of aligning NM_207411.5 with genomic reference NC_000008.10"
],
"variant_exonic_positions": {
"NC_000008.10": {
"end_exon": "7",
"start_exon": "7"
},
"NC_000008.11": {
"end_exon": "7",
"start_exon": "7"
}
}
},
"NM_001289973.2:c.380C>T": {
"alt_genomic_loci": [
{
"grch38": {
"hgvs_genomic_description": "NW_018654717.1:g.211129G>A",
"vcf": {
"alt": "A",
"chr": "HG76_PATCH",
"pos": "211129",
"ref": "G"
}
}
},
{
"hg38": {
"hgvs_genomic_description": "NW_018654717.1:g.211129G>A",
"vcf": {
"alt": "A",
"chr": "NW_018654717.1",
"pos": "211129",
"ref": "G"
}
}
}
],
"annotations": {
"chromosome": "8",
"db_xref": {
"CCDS": null,
"ensemblgene": null,
"hgnc": "HGNC:20782",
"ncbigene": "389610",
"select": false
},
"ensembl_select": false,
"mane_plus_clinical": false,
"mane_select": false,
"map": "8p23.1",
"note": "XK related 5",
"refseq_select": false,
"variant": "2"
},
"gene_ids": {
"ccds_ids": [
"CCDS47763"
],
"ensembl_gene_id": "ENSG00000275591",
"entrez_gene_id": "389610",
"hgnc_id": "HGNC:20782",
"omim_id": [],
"ucsc_id": "uc033baq.2"
},
"gene_symbol": "XKR5",
"genome_context_intronic_sequence": "",
"hgvs_lrg_transcript_variant": "",
"hgvs_lrg_variant": "",
"hgvs_predicted_protein_consequence": {
"lrg_slr": "",
"lrg_tlr": "",
"slr": "NP_001276902.1:p.(S127L)",
"tlr": "NP_001276902.1:p.(Ser127Leu)"
},
"hgvs_refseqgene_variant": "",
"hgvs_transcript_variant": "NM_001289973.2:c.380C>T",
"primary_assembly_loci": {
"grch37": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6673378",
"ref": "AG"
}
},
"grch38": {
"hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6815857",
"ref": "G"
}
},
"hg19": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6673378",
"ref": "AG"
}
},
"hg38": {
"hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6815857",
"ref": "G"
}
}
},
"reference_sequence_records": {
"protein": "https://www.ncbi.nlm.nih.gov/nuccore/NP_001276902.1",
"transcript": "https://www.ncbi.nlm.nih.gov/nuccore/NM_001289973.2"
},
"refseqgene_context_intronic_sequence": "",
"selected_assembly": "hg19",
"submitted_variant": "NC_000008.10:g.6673379del",
"transcript_description": "Homo sapiens XK related 5 (XKR5), transcript variant 2, mRNA",
"validation_warnings": [
"Caution should be used when reporting the displayed variant descriptions: If you are unsure, please contact admin",
"The displayed variants may be artefacts of aligning NM_001289973.1 with genomic reference NC_000008.10",
"The displayed variants may be artefacts of aligning NM_001289973.2 with genomic reference NC_000008.10",
"The displayed variants may be artefacts of aligning NM_207411.4 with genomic reference NC_000008.10",
"A more recent version of the selected reference sequence NM_207411.4 is available (NM_207411.5): NM_207411.5:c.869C>T MUST be fully validated prior to use in reports: select_variants=NM_207411.5:c.869C>T",
"The displayed variants may be artefacts of aligning NM_207411.5 with genomic reference NC_000008.10"
],
"variant_exonic_positions": {
"NC_000008.10": {
"end_exon": "7",
"start_exon": "7"
},
"NC_000008.11": {
"end_exon": "7",
"start_exon": "7"
}
}
},
"NM_207411.4:c.869C>T": {
"alt_genomic_loci": [],
"annotations": {
"chromosome": "8",
"db_xref": {
"CCDS": "CCDS47763.2",
"ensemblgene": null,
"hgnc": "HGNC:20782",
"ncbigene": "389610",
"select": "RefSeq"
},
"ensembl_select": false,
"mane_plus_clinical": false,
"mane_select": false,
"map": "8p23.1",
"note": "XK related 5",
"refseq_select": true,
"variant": "1"
},
"gene_ids": {
"ccds_ids": [
"CCDS47763"
],
"ensembl_gene_id": "ENSG00000275591",
"entrez_gene_id": "389610",
"hgnc_id": "HGNC:20782",
"omim_id": [],
"ucsc_id": "uc033baq.2"
},
"gene_symbol": "XKR5",
"genome_context_intronic_sequence": "",
"hgvs_lrg_transcript_variant": "",
"hgvs_lrg_variant": "",
"hgvs_predicted_protein_consequence": {
"lrg_slr": "",
"lrg_tlr": "",
"slr": "NP_997294.3:p.(S290L)",
"tlr": "NP_997294.3:p.(Ser290Leu)"
},
"hgvs_refseqgene_variant": "",
"hgvs_transcript_variant": "NM_207411.4:c.869C>T",
"primary_assembly_loci": {
"grch37": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6673378",
"ref": "AG"
}
},
"grch38": {
"hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6815857",
"ref": "G"
}
},
"hg19": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6673378",
"ref": "AG"
}
},
"hg38": {
"hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6815857",
"ref": "G"
}
}
},
"reference_sequence_records": {
"protein": "https://www.ncbi.nlm.nih.gov/nuccore/NP_997294.3",
"transcript": "https://www.ncbi.nlm.nih.gov/nuccore/NM_207411.4"
},
"refseqgene_context_intronic_sequence": "",
"selected_assembly": "hg19",
"submitted_variant": "NC_000008.10:g.6673379del",
"transcript_description": "Homo sapiens XK related 5 (XKR5), transcript variant 1, mRNA",
"validation_warnings": [
"Caution should be used when reporting the displayed variant descriptions: If you are unsure, please contact admin",
"The displayed variants may be artefacts of aligning NM_001289973.1 with genomic reference NC_000008.10",
"A more recent version of the selected reference sequence NM_001289973.1 is available (NM_001289973.2): NM_001289973.2:c.380C>T MUST be fully validated prior to use in reports: select_variants=NM_001289973.2:c.380C>T",
"The displayed variants may be artefacts of aligning NM_001289973.2 with genomic reference NC_000008.10",
"The displayed variants may be artefacts of aligning NM_207411.4 with genomic reference NC_000008.10",
"A more recent version of the selected reference sequence NM_207411.4 is available (NM_207411.5): NM_207411.5:c.869C>T MUST be fully validated prior to use in reports: select_variants=NM_207411.5:c.869C>T",
"The displayed variants may be artefacts of aligning NM_207411.5 with genomic reference NC_000008.10"
],
"variant_exonic_positions": {
"NC_000008.10": {
"end_exon": "6",
"start_exon": "6"
},
"NC_000008.11": {
"end_exon": "6",
"start_exon": "6"
}
}
},
"NM_207411.5:c.869C>T": {
"alt_genomic_loci": [
{
"grch38": {
"hgvs_genomic_description": "NW_018654717.1:g.211129G>A",
"vcf": {
"alt": "A",
"chr": "HG76_PATCH",
"pos": "211129",
"ref": "G"
}
}
},
{
"hg38": {
"hgvs_genomic_description": "NW_018654717.1:g.211129G>A",
"vcf": {
"alt": "A",
"chr": "NW_018654717.1",
"pos": "211129",
"ref": "G"
}
}
}
],
"annotations": {
"chromosome": "8",
"db_xref": {
"CCDS": "CCDS47763.2",
"ensemblgene": null,
"hgnc": "HGNC:20782",
"ncbigene": "389610",
"select": "MANE"
},
"ensembl_select": false,
"mane_plus_clinical": false,
"mane_select": true,
"map": "8p23.1",
"note": "XK related 5",
"refseq_select": true,
"variant": "1"
},
"gene_ids": {
"ccds_ids": [
"CCDS47763"
],
"ensembl_gene_id": "ENSG00000275591",
"entrez_gene_id": "389610",
"hgnc_id": "HGNC:20782",
"omim_id": [],
"ucsc_id": "uc033baq.2"
},
"gene_symbol": "XKR5",
"genome_context_intronic_sequence": "",
"hgvs_lrg_transcript_variant": "",
"hgvs_lrg_variant": "",
"hgvs_predicted_protein_consequence": {
"lrg_slr": "",
"lrg_tlr": "",
"slr": "NP_997294.3:p.(S290L)",
"tlr": "NP_997294.3:p.(Ser290Leu)"
},
"hgvs_refseqgene_variant": "",
"hgvs_transcript_variant": "NM_207411.5:c.869C>T",
"primary_assembly_loci": {
"grch37": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6673378",
"ref": "AG"
}
},
"grch38": {
"hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
"vcf": {
"alt": "A",
"chr": "8",
"pos": "6815857",
"ref": "G"
}
},
"hg19": {
"hgvs_genomic_description": "NC_000008.10:g.6673379del", # These are now dels as expected
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6673378",
"ref": "AG"
}
},
"hg38": {
"hgvs_genomic_description": "NC_000008.11:g.6815857G>A",
"vcf": {
"alt": "A",
"chr": "chr8",
"pos": "6815857",
"ref": "G"
}
}
},
"reference_sequence_records": {
"protein": "https://www.ncbi.nlm.nih.gov/nuccore/NP_997294.3",
"transcript": "https://www.ncbi.nlm.nih.gov/nuccore/NM_207411.5"
},
"refseqgene_context_intronic_sequence": "",
"selected_assembly": "hg19",
"submitted_variant": "NC_000008.10:g.6673379del",
"transcript_description": "Homo sapiens XK related 5 (XKR5), transcript variant 1, mRNA",
"validation_warnings": [
"Caution should be used when reporting the displayed variant descriptions: If you are unsure, please contact admin",
"The displayed variants may be artefacts of aligning NM_001289973.1 with genomic reference NC_000008.10",
"A more recent version of the selected reference sequence NM_001289973.1 is available (NM_001289973.2): NM_001289973.2:c.380C>T MUST be fully validated prior to use in reports: select_variants=NM_001289973.2:c.380C>T",
"The displayed variants may be artefacts of aligning NM_001289973.2 with genomic reference NC_000008.10",
"The displayed variants may be artefacts of aligning NM_207411.4 with genomic reference NC_000008.10",
"The displayed variants may be artefacts of aligning NM_207411.5 with genomic reference NC_000008.10"
],
"variant_exonic_positions": {
"NC_000008.10": {
"end_exon": "6",
"start_exon": "6"
},
"NC_000008.11": {
"end_exon": "6",
"start_exon": "6"
}
}
},
"flag": "gene_variant",
"metadata": {
"variantvalidator_hgvs_version": "2.0.2.dev1+g6ecbf8e",
"variantvalidator_version": "1.0.5.dev275+ge591818.d20220711",
"vvdb_version": "vvdb_2022_04",
"vvseqrepo_db": "VV_SR_2022_02/master",
"vvta_version": "vvta_2022_02"
}
}