ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2870A>G (p.Asn957Ser)

dbSNP: rs1555282918
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566925 SCV000664818 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-13 criteria provided, single submitter clinical testing The p.N957S variant (also known as c.2870A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 2870. The asparagine at codon 957 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other 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.
Color Diagnostics, LLC DBA Color Health RCV000566925 SCV000913070 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000799838 SCV000939520 uncertain significance Hereditary breast ovarian cancer syndrome 2018-12-13 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. This sequence change replaces asparagine with serine at codon 957 of the BRCA2 protein (p.Asn957Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. 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. ClinVar contains an entry for this variant (Variation ID: 480896). 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 serine 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 and their clinical significance is uncertain.
University of Washington Department of Laboratory Medicine, University of Washington RCV000566925 SCV003850194 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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