ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5098G>A (p.Gly1700Ser) (rs80358733)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044554 SCV000072567 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 1700 of the BRCA2 protein (p.Gly1700Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. 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: 51766). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Ambry Genetics RCV000221190 SCV000275120 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-26 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000484596 SCV000565832 uncertain significance not provided 2018-04-05 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5098G>A at the cDNA level, p.Gly1700Ser (G1700S) at the protein level, and results in the change of a Glycine to a Serine (GGT>AGT). Using alternate nomenclature, this variant would be defined as BRCA2 5326G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Gly1700Ser was not observed in large population cohorts (Lek 2016). This variant is located in the RAD51 binding domain and the POLH binding domain (Roy 2012, Buisson 2014). 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 Gly1700Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000221190 SCV000911040 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-16 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113378 SCV000146535 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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