ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1865C>T (p.Ala622Val) (rs80358477)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129337 SCV000184100 likely benign Hereditary cancer-predisposing syndrome 2017-03-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000031348 SCV000145969 uncertain significance Breast-ovarian cancer, familial 2 2001-10-29 no assertion criteria provided clinical testing
Color RCV000129337 SCV000911435 likely benign Hereditary cancer-predisposing syndrome 2016-11-21 criteria provided, single submitter clinical testing
GeneDx RCV000430639 SCV000518110 likely benign not specified 2017-10-20 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.
Invitae RCV000043913 SCV000071926 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-12-22 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 622 of the BRCA2 protein (p.Ala622Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs80358477, ExAC <0.01%) but has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 37767). 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"). Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare missense change with uncertain impact on protein function and mRNA splicing. There is no indication that this variant causes disease, but the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000430639 SCV000600491 uncertain significance not specified 2017-03-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031348 SCV000053953 likely benign Breast-ovarian cancer, familial 2 2009-06-19 no assertion criteria provided clinical testing

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