ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9670A>G (p.Ile3224Val)

dbSNP: rs374321381
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000694085 SCV000822512 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3224 of the BRCA2 protein (p.Ile3224Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 96888). 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 RCV001019614 SCV001180995 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-13 criteria provided, single submitter clinical testing The p.I3224V variant (also known as c.9670A>G), located in coding exon 26 of the BRCA2 gene, results from an A to G substitution at nucleotide position 9670. The isoleucine at codon 3224 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in one individual from a Brazilian cohort of women with a personal and/or family history of breast cancer (Pereira JZ et al. Mol Biol Rep, 2022 Oct;49:9509-9520). 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.
Color Diagnostics, LLC DBA Color Health RCV001019614 SCV001343439 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-15 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 3224 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284597 SCV001470465 uncertain significance not provided 2021-05-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000083009 SCV004846214 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 3224 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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) RCV000083009 SCV000115083 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2007-07-10 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.