ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1472C>G (p.Thr491Ser) (rs397507268)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000220125 SCV000279585 likely benign not specified 2017-08-25 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000566123 SCV000668659 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Invitae RCV000637774 SCV000759252 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-10-23 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 491 of the BRCA2 protein (p.Thr491Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in at least one individual affected with breast cancer (PMID: 20104584). ClinVar contains an entry for this variant (Variation ID: 37742). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; 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) RCV000031323 SCV000053928 likely benign Breast-ovarian cancer, familial 2 2010-03-11 no assertion criteria provided clinical testing

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