ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1709A>G (p.Asn570Ser) (rs431825284)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767150 SCV000566304 uncertain significance not provided 2018-06-04 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1709A>G at the cDNA level, p.Asn570Ser (N570S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). Using alternate nomenclature, this variant would be defined as BRCA2 1937A>G. This variant has been reported in at least one individual with breast cancer (Briceno-Balcazar 2017). BRCA2 Asn570Ser was not observed in large population cohorts (Lek 2016). This variant 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 Asn570Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000482766 SCV000591761 uncertain significance not specified 2014-07-24 criteria provided, single submitter clinical testing
Invitae RCV000637388 SCV000758844 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 570 of the BRCA2 protein (p.Asn570Ser). 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 been observed in an individual affected with breast cancer (PMID: 29021639). ClinVar contains an entry for this variant (Variation ID: 96768). 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. 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.
Sharing Clinical Reports Project (SCRP) RCV000082889 SCV000114963 uncertain significance Breast-ovarian cancer, familial 2 2010-04-28 no assertion criteria provided clinical testing

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