Submissions for variant NM_000059.4(BRCA2):c.9401G>T (p.Gly3134Val)

dbSNP: rs80359215

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000254758	SCV000322489	uncertain significance	not provided	2023-03-31	criteria provided, single submitter	clinical testing	Observed in individuals with a personal and/or family history of breast, prostate, or other cancers (Fackenthal et al., 2012; Li et al., 2020; Matejcic et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 9629G>T; This variant is associated with the following publications: (PMID: 22034289, 19043619, 31131967, 32377563, 29884841, 31853058, 32832836, 12228710, 31911673)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000472619	SCV000549833	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-04-22	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3134 of the BRCA2 protein (p.Gly3134Val). This variant is present in population databases (rs80359215, gnomAD 0.006%). This missense change has been observed in individual(s) with breast cancer (PMID: 22034289). ClinVar contains an entry for this variant (Variation ID: 126211). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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	RCV001019281	SCV001180616	uncertain significance	Hereditary cancer-predisposing syndrome	2022-09-19	criteria provided, single submitter	clinical testing	The p.G3134V variant (also known as c.9401G>T), located in coding exon 24 of the BRCA2 gene, results from a G to T substitution at nucleotide position 9401. The glycine at codon 3134 is replaced by valine, an amino acid with dissimilar properties. This alteration was detected in 1/434 Nigerian breast cancer patients (Fackenthal JD et al. Int J Cancer. 2012 Sep 1;131(5):1114-23). This variant was also identified in a cohort of 3,579 African males diagnosed with prostate cancer who underwent multi-gene panel testing of 19 DNA repair and cancer predisposition genes (Matejcic M et al. JCO Precis Oncol, 2020 Jan;4:32-43). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV001019281	SCV001354227	uncertain significance	Hereditary cancer-predisposing syndrome	2021-07-19	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with valine at codon 3134 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 22034289). This variant has been identified in 1/251350 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics	RCV003474706	SCV004211801	uncertain significance	Familial cancer of breast	2023-10-27	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000114104	SCV000147629	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing