ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.566A>G (p.Asp189Gly) (rs397507359)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542458 SCV000635463 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-05-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 189 of the BRCA2 protein (p.Asp189Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 37986). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on BRCA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000567705 SCV000673116 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Sharing Clinical Reports Project (SCRP) RCV000031567 SCV000054172 uncertain significance Breast-ovarian cancer, familial 2 2011-07-15 no assertion criteria provided clinical testing
Pathway Genomics RCV000031567 SCV000223759 uncertain significance Breast-ovarian cancer, familial 2 2014-10-30 no assertion criteria provided clinical testing

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