ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6151A>G (p.Asn2051Asp)

dbSNP: rs1555284569
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508232 SCV000600681 uncertain significance not specified 2016-09-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000637423 SCV000758880 uncertain significance Hereditary breast ovarian cancer syndrome 2018-01-31 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 aspartic acid 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. ClinVar contains an entry for this variant (Variation ID: 438993). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with aspartic acid at codon 2051 of the BRCA2 protein (p.Asn2051Asp). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and aspartic acid.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157629 SCV003850978 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 RCV003157629 SCV005548641 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-22 criteria provided, single submitter clinical testing The p.N2051D variant (also known as c.6151A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6151. The asparagine at codon 2051 is replaced by aspartic acid, an amino acid with highly 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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