ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9271G>A (p.Val3091Ile) (rs80359194)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165867 SCV000216616 likely benign Hereditary cancer-predisposing syndrome 2017-04-11 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000083157 SCV000147595 uncertain significance Breast-ovarian cancer, familial 2 2002-12-23 no assertion criteria provided clinical testing
Color RCV000165867 SCV000911042 benign Hereditary cancer-predisposing syndrome 2017-01-22 criteria provided, single submitter clinical testing
Counsyl RCV000083157 SCV000489188 uncertain significance Breast-ovarian cancer, familial 2 2016-09-01 criteria provided, single submitter clinical testing
GeneDx RCV000045772 SCV000210685 likely benign not specified 2017-07-13 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 RCV000590012 SCV000695230 uncertain significance not provided 2017-07-03 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9271G>A (p.Val3091Ile) variant involves the alteration of a conserved nucleotide located in the Nucleic acid-binding, OB-fold domain (InterPro). 2/3 in silico tools predict a benign outcome for this variant. This variant is absent in 113852 control chromosomes. This variant was found in several HBOC patients/families and one gastric adenocarcinoma patient without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this likely benign, without evidence to independently evaluate. In functional studies, this variant displayed increased homologous recombination, however, the cause-effect relation between this effect and HBOC is unclear and results/explanations by authors are contradicting. Considering all data available at this time, there is insufficient evidence to establish the clinical significance of this variant with confidence. Therefore the variant was classified as VUS until more data becomes available.
Invitae RCV000167774 SCV000073785 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-01 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 3091 of the BRCA2 protein (p.Val3091Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with breast cancer (PMID: 21671020, 24916970). Segregation studies have not been reported for this variant. This variant is also known as 9499G>A. ClinVar contains an entry for this variant (Variation ID: 52798). Experimental studies present conflicting results regarding the impact that this missense change has on BRCA2 homologous recombination activity (PMID: 21671020, 23328489, 29884841). The clinical significance of these findings is unclear. 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.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045772 SCV000587994 uncertain significance not specified 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000083157 SCV000115231 likely benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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