Merge pull request #443 from openvar/update_to_vvta

bug fix for #419 an…

Author: Peter J. Freeman

VariantValidator/modules/mappers.py

@@ -37,6 +37,16 @@ def gene_to_transcripts(variant, validator, select_transcripts_dict):
 
     # Set test to see if Norm alters the coords
     g_test = variant.hn.normalize(g_query)
+    try:
+        if "N" in g_test.posedit.edit.ref:
+            variant.warnings.append("Submitted variant description cannot be validated as it is located in a region of "
+                                    "the reference sequence represented by base 'N' and not 'GATC'")
+            logger.warning(error)
+            return True
+    except AttributeError:
+        pass
+    except TypeError:
+        pass
 
     # Perform test
     if g_query.posedit.pos != g_test.posedit.pos:
@@ -389,6 +399,7 @@ def transcripts_to_gene(variant, validator, select_transcripts_dict_plus_version
                     return True
                 else:
                     logger.debug("Except passed, %s", e)
+
             # genome back to C coordinates
             try:
                 post_var = validator.myevm_g_to_t(variant.evm, pre_var, trans_acc)
@@ -397,13 +408,12 @@ def transcripts_to_gene(variant, validator, select_transcripts_dict_plus_version
                 logger.warning(str(error))
                 return True
             test = validator.hp.parse_hgvs_variant(quibble_input)
-
             if post_var.posedit.pos.start.base != test.posedit.pos.start.base or \
                     post_var.posedit.pos.end.base != test.posedit.pos.end.base:
-                caution = 'The entered coordinates do not agree with the intron/exon boundaries for the ' \
-                          'selected transcript'
+                caution = "ExonBoundaryError: Position c.%s does not correspond with an exon boundary for transcript " \
+                          "%s" % (test.posedit.pos, test.ac)
                 variant.warnings.extend([caution])
-                # raise MappersError(caution)
+                raise MappersError(caution)
 
         else:  # del not in formatted_variant
 
@@ -415,14 +425,13 @@ def transcripts_to_gene(variant, validator, select_transcripts_dict_plus_version
 
             # genome back to C coordinates
             post_var = validator.myevm_g_to_t(variant.evm, pre_var, trans_acc)
-
             test = validator.hp.parse_hgvs_variant(quibble_input)
             if post_var.posedit.pos.start.base != test.posedit.pos.start.base or \
                     post_var.posedit.pos.end.base != test.posedit.pos.end.base:
-                caution = 'The entered coordinates do not agree with the intron/exon boundaries for the ' \
-                          'selected transcript'
+                caution = "ExonBoundaryError: Position c.%s does not correspond with an exon boundary for transcript " \
+                          "%s" % (test.posedit.pos, test.ac)
                 variant.warnings.extend([caution])
-                # raise MappersError(caution)
+                raise MappersError(caution)
 
     elif ':g.' not in quibble_input:
         query = validator.hp.parse_hgvs_variant(formatted_variant)

VariantValidator/modules/use_checking.py

@@ -347,8 +347,6 @@ def structure_checks_c(variant, validator):
         try:
             validator.vr.validate(variant.input_parses)
         except vvhgvs.exceptions.HGVSInvalidVariantError as e:
-            print("The error")
-            print(e)
             error = str(e)
             if 'bounds' in error:
                 try:
@@ -388,7 +386,7 @@ def structure_checks_c(variant, validator):
             if (variant.input_parses.posedit.pos.end.base > int(tx_info[4]) or variant.input_parses.posedit.pos.end.base
                 > int(tx_info[4])) and ("*" not in str(variant.input_parses.posedit.pos.end) or "*" not in
                                         str(variant.input_parses.posedit.pos.start)):
-                errors = ["Variant start position and/or end position are beyond the CDS end position "
+                errors = ["CDSError: Variant start position and/or end position are beyond the CDS end position "
                           "and likely also beyond the end of the selected reference sequence"]
             else:
                 errors = ['Required information for ' + variant.input_parses.ac + ' is missing from the Universal '

VariantValidator/modules/vvMixinCore.py

@@ -666,8 +666,9 @@ def validate(self,
                                 logger.warning(error)
                                 continue
 
-                    elif my_variant.hgvs_formatted.posedit.pos.end.base < my_variant.hgvs_formatted.posedit.pos.start.base:
-                        if "NC_012920.1" not in my_variant.hgvs_formatted.ac and\
+                    elif my_variant.hgvs_formatted.posedit.pos.end.base < \
+                            my_variant.hgvs_formatted.posedit.pos.start.base:
+                        if "NC_012920.1" not in my_variant.hgvs_formatted.ac and \
                                 "NC_001807.4" not in my_variant.hgvs_formatted.ac:
                             error = 'Interval end position ' + str(my_variant.hgvs_formatted.posedit.pos.end.base) + \
                                     ' < interval start position ' + str(my_variant.hgvs_formatted.posedit.pos.start.base)

tests/test_warnings.py

@@ -22,8 +22,8 @@ def test_issue_169(self):
         variant = 'NC_000017.10(NM_007294.3):c.4421-63A>G'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-        assert 'The entered coordinates do not agree with the intron/exon boundaries for the selected transcript' in \
-               results['validation_warning_1']['validation_warnings'][0]
+        assert 'ExonBoundaryError: Position c.4421-63 does not correspond with an exon boundary for transcript NM_007294.3' in \
+               results['validation_warning_1']['validation_warnings']
 
     def test_issue_176(self):
         variant = 'NC_000023.10(NM_004006.2):c.8810A>G'
@@ -600,15 +600,13 @@ def test_vv_series_1(self):
         variant = 'NC_000004.11:g.140811117C>A'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_018717.4 contains 3 fewer bases between c.2276_2277, and 12 fewer bases between c.1467_1468 than NC_000004.11" in \
                results['NM_018717.4:c.1472_1473insTCAGCAGCAGCA']['validation_warnings']
 
     def test_vv_series_2(self):
         variant = 'NC_000008.10:g.24811072C>T'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_006158.5 contains 1 fewer bases between c.1413_1414 than NC_000008.10" in \
                results['NM_006158.5:c.1407delinsAC']['validation_warnings']
         assert "NM_006158.4 contains 1 fewer bases between c.1407_1408 than NC_000008.10" in \
@@ -620,7 +618,6 @@ def test_vv_series_3(self):
         variant = 'NC_000015.9:g.72105933del'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_016346.4 contains 1 fewer bases between c.951_952 than NC_000015.9" in \
                results['NM_016346.4:c.951_952=']['validation_warnings']
         assert "NM_016346.3 contains 1 fewer bases between c.947_948 than NC_000015.9" in \
@@ -638,7 +635,6 @@ def test_vv_series_4(self):
         variant = 'NC_000019.9:g.41123095dup'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_003573.2 contains 1 extra bases between c.3122_3124 than NC_000019.9" in \
                results['NM_003573.2:c.3122_3124=']['validation_warnings']
         assert "NM_001042545.2 contains 1 extra bases between c.3034_3036 than NC_000019.9" in \
@@ -652,7 +648,6 @@ def test_vv_series_5(self):
         variant = 'NC_000017.10:g.5286863_5286889AGTGTTTGGAATTTTCTGTTCATATAG='
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_004703.6 contains 25 fewer bases between c.*369_*370 than NC_000017.10" in \
                results['NM_004703.6:c.*344_*368dup']['validation_warnings']
         assert "NM_004703.5 contains 25 fewer bases between c.*344_*345 than NC_000017.10" in \
@@ -674,15 +669,13 @@ def test_vv_series_6(self):
         variant = 'NC_000012.11:g.122064777C>A'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_032790.3 contains 6 fewer bases between c.126_127 than NC_000012.11" in \
                results['NM_032790.3:c.129_130insACACCG']['validation_warnings']
 
     def test_vv_series_7(self):
         variant = 'NC_000002.11:g.95847041_95847043GCG='
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_021088.3 contains 3 fewer bases between c.467_468 than NC_000002.11" in \
                results['NM_021088.3:c.471_473dup']['validation_warnings']
         assert "NM_021088.2 contains 3 fewer bases between c.467_468 than NC_000002.11" in \
@@ -702,7 +695,6 @@ def test_vv_series_8(self):
         variant = 'NC_000003.11:g.14561629_14561630insG'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_001080423.4 contains 1 extra bases between c.1019_1021 than NC_000003.11" in \
                results['NM_001080423.4:c.1019_1021=']['validation_warnings']
         assert "NM_001080423.3 contains 1 extra bases between c.1017_1019 than NC_000003.11" in \
@@ -714,15 +706,13 @@ def test_vv_series_9(self):
         variant = 'NC_000004.11:g.140811117C>A'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_018717.4 contains 3 fewer bases between c.2276_2277, and 12 fewer bases between c.1467_1468 than NC_000004.11" in \
                results['NM_018717.4:c.1472_1473insTCAGCAGCAGCA']['validation_warnings']
 
     def test_vv_series_10(self):
         variant = 'NC_000009.11:g.136132908_136132909TA='
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_020469.3 contains 22 extra bases between c.*756_*757, and 2 extra bases between c.*797_*798, and 110 extra bases between c.*840_*841, and 2 extra bases between c.*4648_*4649, and 1 extra bases between c.260_262 than NC_000009.11" in \
                results['NM_020469.3:c.261del']['validation_warnings']
         assert "NM_020469.2 contains 1 extra bases between c.260_262 than NC_000009.11" in \
@@ -732,7 +722,6 @@ def test_vv_series_11(self):
         variant = 'NC_000019.10:g.50378563_50378564insTAC'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_007121.5 contains 3 extra bases between c.514_518 than NC_000019.10" in \
                results['NM_007121.5:c.515A>T']['validation_warnings']
         assert "NM_001256647.1 contains 3 extra bases between c.223_227 than NC_000019.10" in \
@@ -742,18 +731,30 @@ def test_vv_series_12(self):
         variant = 'NC_000007.13:g.149476664_149476666delinsTC'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NR_163594.1 contains 1 extra bases between n.1129_1131, and 1 fewer bases between n.11675_11676 than NC_000007.13" in \
                results['NR_163594.1:n.1122_1124delinsT']['validation_warnings']
 
     def test_vv_series_13(self):
         variant = 'NC_000004.12:g.139889957_139889968del'
         results = self.vv.validate(variant, 'GRCh37', 'all').format_as_dict(test=True)
         print(results)
-
         assert "NM_018717.4 contains 3 fewer bases between c.2276_2277, and 12 fewer bases between c.1467_1468 than NC_000004.12" in \
                results['NM_018717.4:c.1466_1468=']['validation_warnings']
 
+    def test_vv_series_14(self):
+        variant = 'NM_000516.7:c.2780+73C>T'
+        results = self.vv.validate(variant, 'GRCh38', 'all').format_as_dict(test=True)
+        print(results)
+        assert "CDSError: Variant start position and/or end position are beyond the CDS end position and likely also beyond the end of the selected reference sequence" in \
+               results['validation_warning_1']['validation_warnings']
+
+    def test_vv_series_15(self):
+        variant = 'NM_000518.5:c.89+25del'
+        results = self.vv.validate(variant, 'GRCh38', 'all').format_as_dict(test=True)
+        print(results)
+        assert "ExonBoundaryError: Position c.89+25 does not correspond with an exon boundary for transcript NM_000518.5" in \
+               results['validation_warning_1']['validation_warnings']
+
 
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