ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2176del (p.Val726fs) (rs1555282499)

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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 RCV000586698 SCV000694593 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-11 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2176delG (p.Val726Phefs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 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 (e.g. c.2212dupT (p.Cys738fs), c.2287delC (p.His763fs), and c.2330dupA (p.Asp777fs)). The variant of interest has not been reported in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications. One reputable database cites the variant with a classification of "Causal." Therefore, the variant of interest has been classified as Likely Pathogenic until additional information becomes available.
Invitae RCV000586698 SCV001394965 pathogenic Hereditary breast and ovarian cancer syndrome 2019-07-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val726Phefs*4) 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 been observed in an individual with personal and family history of breast and/or ovarian cancer (PMID: 28294317). ClinVar contains an entry for this variant (Variation ID: 495437). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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