ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2650T>G (p.Ser884Ala)

dbSNP: rs1555282771
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000549818 SCV000635235 uncertain significance Hereditary breast ovarian cancer syndrome 2021-03-18 criteria provided, single submitter clinical testing 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 alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. 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. This sequence change replaces serine with alanine at codon 884 of the BRCA2 protein (p.Ser884Ala). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and alanine.
Ambry Genetics RCV002456094 SCV002739042 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-17 criteria provided, single submitter clinical testing The p.S884A variant (also known as c.2650T>G), located in coding exon 10 of the BRCA2 gene, results from a T to G substitution at nucleotide position 2650. The serine at codon 884 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002456094 SCV003848474 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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