ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8169T>A (p.Asp2723Glu) (rs1060502432)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568974 SCV000666072 likely pathogenic Hereditary cancer-predisposing syndrome 2016-07-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000568974 SCV000910281 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-12 criteria provided, single submitter clinical testing
Invitae RCV000467822 SCV000549619 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-08-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 2723 of the BRCA2 protein (p.Asp2723Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. 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: 409493). 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. Variants that disrupt the p.Asp2723 amino acid residue in BRCA2 have been observed in affected individuals (PMID: 15290653, 16489001, 11207042, 23961350, 24728189, 25452441). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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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