ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3001T>G (p.Ser1001Ala)

dbSNP: rs2137492111
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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 RCV002009966 SCV002283964 uncertain significance Hereditary breast ovarian cancer syndrome 2021-03-08 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. 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. This sequence change replaces serine with alanine at codon 1001 of the BRCA2 protein (p.Ser1001Ala). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and alanine.
University of Washington Department of Laboratory Medicine, University of Washington RCV003156986 SCV003850303 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).
Ambry Genetics RCV003156986 SCV004005380 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-19 criteria provided, single submitter clinical testing The p.S1001A variant (also known as c.3001T>G), located in coding exon 10 of the BRCA2 gene, results from a T to G substitution at nucleotide position 3001. The serine at codon 1001 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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.

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