ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1219C>T (p.Gln407Ter) (rs781079248)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547485 SCV000635147 pathogenic Hereditary breast and ovarian cancer syndrome 2020-03-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln407*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 462226). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Color Health, Inc RCV000583844 SCV000688700 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000583844 SCV001170594 pathogenic Hereditary cancer-predisposing syndrome 2018-08-06 criteria provided, single submitter clinical testing The p.Q407* pathogenic mutation (also known as c.1219C>T), located in coding exon 9 of the BRCA2 gene, results from a C to T substitution at nucleotide position 1219. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000547485 SCV001554632 likely pathogenic Hereditary breast and ovarian cancer syndrome 2021-03-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1219C>T (p.Gln407X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250212 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1219C>T in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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