ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9839C>G (p.Pro3280Arg) (rs80359246)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000588196 SCV000695275 uncertain significance not provided 2017-03-03 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9839C>G (p.Pro3280Arg) variant involves the alteration of a conserved nucleotide. The variant is not found within a known functional domain of the protein (InterPro). 5/5 in silico tools predict a damaging outcome for this variant. This variant is absent from the large control population database ExAC (0/121382 control chromosomes). To our knowledge, the variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000704666 SCV000833622 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-23 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 3280 of the BRCA2 protein (p.Pro3280Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. 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: 495523). 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 disruptive, but 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.

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