ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9035C>G (p.Ala3012Gly) (rs768335521)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456830 SCV000549543 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 3012 of the BRCA2 protein (p.Ala3012Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (ExAC no frequency) and 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000589531 SCV000695201 uncertain significance not provided 2017-02-06 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9035C>G (p.Ala3012Gly) variant involves the alteration of a conserved nucleotide and is predicted to be benign by 2/4 in silico tools (SNPs&GO not captured due to low reliability index). This variant is absent in 120524 control chromosomes from ExAC. The variant of interest has not, to our knowledge, been reported in affected individuals as a germline variant 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.

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