ClinVar Miner

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

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129373 SCV000184137 likely benign Hereditary cancer-predisposing syndrome 2018-02-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign)
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761164 SCV000891080 uncertain significance Large Cell/Anaplastic Medulloblastoma 2017-04-03 no assertion criteria provided clinical testing
Color RCV000129373 SCV000903031 benign Hereditary cancer-predisposing syndrome 2016-11-18 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
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.
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.
Invitae RCV000231063 SCV000283368 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-17 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000144220 SCV000189323 benign Breast-ovarian cancer, familial 2 2012-01-04 no assertion criteria provided clinical testing

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