ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8242G>A (p.Gly2748Ser) (rs56371528)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459448 SCV000549509 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-05-09 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2748 of the BRCA2 protein (p.Gly2748Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 409429). 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. A different missense substitution at this codon (p.Gly2748Asp) has been determined to be pathogenic (Invitae database). This suggests that the glycine residue is critical for BRCA2 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a rare missense change with uncertain impact on protein function. Without additional functional and/or genetic data, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506943 SCV000600792 uncertain significance not specified 2017-02-23 criteria provided, single submitter clinical testing
Color RCV000582320 SCV000689108 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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