ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9433G>C (p.Val3145Leu) (rs587776476)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129373 SCV000184137 likely benign Hereditary cancer-predisposing syndrome 2019-05-02 criteria provided, single submitter clinical testing Other data supporting benign classification;In silico models in agreement (benign)
Invitae RCV001088631 SCV000283368 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000499802 SCV000592287 uncertain significance not specified 2014-01-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590711 SCV000695239 uncertain significance not provided 2016-09-09 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9433G>C (p.Val3145Leu) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. Val3145 is not conserved across species and located in the Nucleic acid-binding, OB-fold domain (Interpro); a Leu residue can be found at this position in zebrafish, suggesting that this missense change is tolerate.This variant was found in 1/121308 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). In addition, multiple clinical diagnostic laboratories classified this variant as likely benign/benign without providing evidence to independently evaluate. Furthermore, this variant was found to co-occur with a pathogenic BRIP1 variant (c.2392C>T; p.R798*) in one LCA internal specimen; however the occurrence of one pathogenic BRIP1 variant may not explain a cancer phenotype, as the pathogenicity of this specific LOF variant in BRIP1 (p.Arg798Ter) in addition to all other truncating variants in regards to their breast cancer risk have recently been called into question (PMID:26921362). Taken together, this variant is classified as VUS until additional information is available.
GeneDx RCV000499802 SCV000715915 likely benign not specified 2017-04-13 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.
Color RCV000129373 SCV000903031 benign Hereditary cancer-predisposing syndrome 2016-11-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000144220 SCV001267534 uncertain significance Breast-ovarian cancer, familial 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001114170 SCV001272016 uncertain significance Fanconi anemia, complementation group D1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sharing Clinical Reports Project (SCRP) RCV000144220 SCV000189323 benign Breast-ovarian cancer, familial 2 2012-01-04 no assertion criteria provided clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761164 SCV000891080 uncertain significance Anaplastic/large cell medulloblastoma 2017-04-03 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.