ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9458G>C (p.Gly3153Ala) (rs80359220)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045825 SCV000073838 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163366 SCV000213903 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-05 criteria provided, single submitter clinical testing The p.G3153A variant (also known as c.9458G>C), located in coding exon 24 of the BRCA2 gene, results from a G to C substitution at nucleotide position 9458. The glycine at codon 3153 is replaced by alanine, an amino acid with similar properties. This alteration was predicted to be neutral by a protein likelihood ratio model (Karchin R et al. Cancer Inform. 2008;6:203-16). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000222193 SCV000279319 likely benign not specified 2017-12-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588545 SCV000695241 uncertain significance not provided 2017-07-03 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9458G>C (p.Gly3153Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a missense change in the nucleic acid-binding, OB-fold domain (InterPro). 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in the large control database ExAC and control cohorts from the literature at a frequency of 0.0000407 (5/122754 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). In the literature, the variant has been identified in one patient with hyperdiploid ALL (Zhang_NEJM_2015), but not breast and/or ovarian cancer. Multiple clinical diagnostic laboratories/reputable databases have conflicting interpretations of the variant, including uncertain significance and likely benign. Taken together, this variant is classified as VUS until additional information becomes available.
Counsyl RCV000114111 SCV000785178 uncertain significance Breast-ovarian cancer, familial 2 2017-05-26 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163366 SCV000903037 likely benign Hereditary cancer-predisposing syndrome 2016-12-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588545 SCV001133982 uncertain significance not provided 2019-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000114111 SCV001139263 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000114111 SCV000147642 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000114111 SCV000297579 likely benign Breast-ovarian cancer, familial 2 2008-11-18 no assertion criteria provided clinical testing

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