ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.770A>C (p.Asn257Thr)

dbSNP: rs587782357
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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 RCV000131305 SCV000186277 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-11 criteria provided, single submitter clinical testing The p.N257T variant (also known as c.770A>C), located in coding exon 8 of the BRCA2 gene, results from an A to C substitution at nucleotide position 770. The asparagine at codon 257 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001056516 SCV001220961 uncertain significance Hereditary breast ovarian cancer syndrome 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with threonine at codon 257 of the BRCA2 protein (p.Asn257Thr). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and threonine. This variant is present in population databases (rs587782357, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRCA2-related conditions. 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 threonine 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. 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.
Color Diagnostics, LLC DBA Color Health RCV000131305 SCV001353449 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-31 criteria provided, single submitter clinical testing

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