ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2444T>A (p.Met815Lys)

dbSNP: rs1303254121
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001229825 SCV001402282 uncertain significance Hereditary breast ovarian cancer syndrome 2019-10-31 criteria provided, single submitter clinical testing 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. 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. This sequence change replaces methionine with lysine at codon 815 of the BRCA2 protein (p.Met815Lys). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and lysine. 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 conditions. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158575 SCV003848320 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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