ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9770_9771del (p.Lys3257fs) (rs1566260997)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779931 SCV000916872 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-29 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9770_9771delAA (p.Lys3257ArgfsX2) 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 (eg., p.Arg3268fsX9 and p.Tyr3308X). The variant was absent in 277164 control chromosomes. To our knowledge, no occurrence of c.9770_9771delAA in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000779931 SCV001388053 pathogenic Hereditary breast and ovarian cancer syndrome 2019-07-01 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BRCA2 gene (p.Lys3257Argfs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 162 amino acids of the BRCA2 protein. 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: 632692). This variant disrupts the C-terminus of the BRCA2 protein. Other variant(s) that disrupt this region (p.Tyr3308*) have been determined to be pathogenic (PMID: 17026620, 22711857, 18593900, 18607349). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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