ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1777G>T (p.Ala593Ser) (rs431825286)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562320 SCV000661337 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000637708 SCV000759180 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-08-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 593 of the BRCA2 protein (p.Ala593Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 96770). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000082891 SCV000114965 uncertain significance Breast-ovarian cancer, familial 2 2009-07-17 no assertion criteria provided clinical testing

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