ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4295G>A (p.Ser1432Asn)

dbSNP: rs1566230025
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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 RCV000694470 SCV000822918 uncertain significance Hereditary breast ovarian cancer syndrome 2018-05-22 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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine 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. This variant has not been reported in the literature in individuals with BRCA2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 1432 of the BRCA2 protein (p.Ser1432Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine.
Ambry Genetics RCV001022228 SCV001183941 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-06 criteria provided, single submitter clinical testing The p.S1432N variant (also known as c.4295G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 4295. The serine at codon 1432 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 RCV001022228 SCV003850392 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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