ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2348T>G (p.Val783Gly)

gnomAD frequency: 0.00001  dbSNP: rs768143929
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167274 SCV000218117 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-12 criteria provided, single submitter clinical testing The p.V783G variant (also known as c.2348T>G), located in coding exon 10 of the BRCA2 gene, results from a T to G substitution at nucleotide position 2348. The valine at codon 783 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well 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.
Counsyl RCV000238666 SCV000487905 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2015-12-13 criteria provided, single submitter clinical testing
Invitae RCV000559193 SCV000635219 likely benign Hereditary breast ovarian cancer syndrome 2023-10-11 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000167274 SCV000911752 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-15 criteria provided, single submitter clinical testing This missense variant replaces valine with glycine at codon 783 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with prostate cancer and in a suspected hereditary breast and ovarian cancer family (PMID: 28259476, 31409081). This variant has also been detected in a breast cancer case-control meta-analysis in 2/53459 unaffected individuals and absent in 60466 cases (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_002356) and in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.0498 and 0.3997, respectively, (PMID: 31131967). This variant has been identified in 1/250824 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174861 SCV001338251 uncertain significance not specified 2022-10-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.2348T>G (p.Val783Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250824 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2348T>G has been reported in the literature in at least one individual affected with suspected Hereditary Breast And Ovarian Cancer Syndrome. This reports does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with other pathogenic variants have been reported (BRCA1 c.5266dup/p.Gln1756ProfsX74 and BRCA1 c.5503C>T/p.R1835*), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign n=2, VUS n=5). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001283917 SCV001469412 uncertain significance not provided 2019-10-23 criteria provided, single submitter clinical testing
GeneDx RCV001283917 SCV001785116 uncertain significance not provided 2022-05-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with prostate cancer (Annala 2017); Also known as 2576T>G; This variant is associated with the following publications: (PMID: 30212499, 31131967, 28259476)
Sema4, Sema4 RCV000167274 SCV002533313 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-21 criteria provided, single submitter curation
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003150029 SCV003838817 uncertain significance Breast and/or ovarian cancer 2021-07-02 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000167274 SCV003848246 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
All of Us Research Program, National Institutes of Health RCV000238666 SCV004847046 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-08-08 criteria provided, single submitter clinical testing This missense variant replaces valine with glycine at codon 783 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with prostate cancer and in a suspected hereditary breast and ovarian cancer family (PMID: 28259476, 31409081). This variant has also been detected in a breast cancer case-control meta-analysis in 2/53459 unaffected individuals and absent in 60466 cases (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_002356) and in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.0498 and 0.3997, respectively, (PMID: 31131967). This variant has been identified in 1/250824 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.
Sharing Clinical Reports Project (SCRP) RCV000238666 SCV000297509 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2013-06-01 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.