ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1764T>G (p.Asn588Lys)

gnomAD frequency: 0.00001  dbSNP: rs1235065739
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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 RCV001013026 SCV001173557 likely benign Hereditary cancer-predisposing syndrome 2019-06-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001860732 SCV002292050 uncertain significance Hereditary breast ovarian cancer syndrome 2022-02-18 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 588 of the BRCA2 protein (p.Asn588Lys). ClinVar contains an entry for this variant (Variation ID: 820012). 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.
University of Washington Department of Laboratory Medicine, University of Washington RCV001013026 SCV003851620 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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