ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.814A>G (p.Asn272Asp) (rs398122598)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486677 SCV000566411 uncertain significance not provided 2018-01-17 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.814A>G at the cDNA level, p.Asn272Asp (N272D) at the protein level, and results in the change of an Asparagine to an Aspartic Acid (AAT>GAT). Using alternate nomenclature, this variant would be defined as BRCA2 1042A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asn272Asp was not observed in large population cohorts (Lek 2016). BRCA2 Asn272Asp is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Asn272Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000529674 SCV000635642 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-07-07 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 272 of the BRCA2 protein (p.Asn272Asp). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and aspartic acid. 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 disease. ClinVar contains an entry for this variant (Variation ID: 91503). 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. 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 RCV000774908 SCV000908930 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-13 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077020 SCV000108817 uncertain significance Breast-ovarian cancer, familial 2 2010-10-05 no assertion criteria provided clinical testing

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