ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9401G>T (p.Gly3134Val) (rs80359215)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254758 SCV000322489 uncertain significance not provided 2018-02-27 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9401G>T at the cDNA level, p.Gly3134Val (G3134V) at the protein level, and results in the change of a Glycine to a Valine (GGC>GTC). Using alternate nomenclature, this variant has been previously published as BRCA2 9629G>T. This variant has been observed in at least one individual with breast cancer (Fackenthal 2012). BRCA2 Gly3134Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glycine and Valine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Gly3134Val occurs at a position that is not conserved and is located in the DNA binding domain (Yang 2002). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Gly3134Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000472619 SCV000549833 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-08 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 3134 of the BRCA2 protein (p.Gly3134Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs80359215, ExAC 0.01%). This variant has been reported in the literature in an individual affected with breast cancer (PMID: 22034289). ClinVar contains an entry for this variant (Variation ID: 126211). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) and an algorithm developed specifically for the BRCA2 (PMID: 19043619) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000114104 SCV000147629 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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