ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9052A>G (p.Ser3018Gly) (rs431825373)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132352 SCV000187441 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000483142 SCV000567094 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9052A>G at the cDNA level, p.Ser3018Gly (S3018G) at the protein level, and results in the change of a Serine to a Glycine (AGT>GGT). Using alternate nomenclature, this variant would be defined as BRCA2 9280A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ser3018Gly was not observed in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Yang 2002). In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA2 Ser3018Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000703275 SCV000832170 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-04-27 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 3018 of the BRCA2 protein (p.Ser3018Gly). The serine residue is weakly conserved and there is a small physicochemical difference between serine and glycine. 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: 96877). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. 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) RCV000082998 SCV000115072 uncertain significance Breast-ovarian cancer, familial 2 2012-09-07 no assertion criteria provided clinical testing

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