ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9285C>A (p.Asp3095Glu) (rs80359198)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812850 SCV000953178 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 3095 of the BRCA2 protein (p.Asp3095Glu). 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 BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 252859). 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 and their clinical significance is uncertain. 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. A different variant (c.9285C>G, or 9513C>G) giving rise to the same protein effect observed here (p.Asp3095Glu) has been reported in many families with supportive evidence of segregation with a BRCA2-related disease (PMID: 18451181, 18951446, 22678057), indicating that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000239130 SCV000297462 pathogenic Breast-ovarian cancer, familial 2 2013-07-17 no assertion criteria provided clinical testing

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