ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10249T>C (p.Tyr3417His) (rs535952730)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474923 SCV000549673 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 3417 of the BRCA2 protein (p.Tyr3417His). The tyrosine residue is weakly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs535952730, ExAC 0.02%) but has not been reported in the literature in individuals with a BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000574730 SCV000668864 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000615202 SCV000724263 likely benign not specified 2017-10-30 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.
Color RCV000574730 SCV000906836 likely benign Hereditary cancer-predisposing syndrome 2017-05-27 criteria provided, single submitter clinical testing

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