ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8881G>A (p.Gly2961Ser) (rs878853614)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564860 SCV000668653 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000564860 SCV000906756 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589058 SCV000695187 uncertain significance not provided 2016-11-07 criteria provided, single submitter clinical testing Variant summary: The c.8881G>A (p.Gly2961Ser) in BRCA2 gene is a missense change that involves a non-conserved nucleotide and 3/4 in silico tools predict benign outcome. The variant is located within the tower domain, however no functional studies confirming the impact of the variant on the protein function were published at the time of evaluation. The variant is absent from the large control population dataset of ExAC. The variant has not, to our knowledge, been reported in affected individuals in the literature, but was cited as VUS by several reputable databases/clinical laboratories. Lastly, this variant was identified in an internal specimen, undergoing genetic testing, together with c.3228_3229delAG in BRCA1 gene. Taking together, the variant was classified as VUS until more data become available.
Invitae RCV000228865 SCV000283353 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-01-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2961 of the BRCA2 protein (p.Gly2961Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with breast cancer in the Leiden Open-source Variation Database (PMID: 21520333). 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 is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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