ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.467A>G (p.Asp156Gly) (rs68071147)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129132 SCV000183850 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
Breast Cancer Information Core (BIC) (BRCA2) RCV000077333 SCV000146918 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129132 SCV000903073 likely benign Hereditary cancer-predisposing syndrome 2016-04-21 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000044468 SCV000588067 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
GeneDx RCV000044468 SCV000210243 likely benign not specified 2017-09-13 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.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000167806 SCV000267841 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-04-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589959 SCV000694795 uncertain significance not provided 2017-07-14 criteria provided, single submitter clinical testing Variant summary: The c.467A>G (p.Asp156Gly) in BRCA2 , causes a missense change involving the alteration of a conserved nucleotide with 3/5 in silico tools predicting a benign outcome. 5/5 programs in Alamut predict that this variant may affect splicing as it generates a cryptic splice site. In concordant to splice-site tools' predictions, RNA studies showed that this variant leads to utilization of the new cryptic splice-site and abnormal splicing product. Direct sequencing of the aberrant transcript revealed a 9bp nucleotide deletion and removing 3 last non-conserved amino acids of exon 5, p.Asp156_Ser158del. From the published data the ratio of wt vs aberrant transcript was ~ 95%:5%, suggesting potential noncontributory of the alternative product. In addition, removed amino acids located outside of any known functional domain or repeat. The variant was observed in the large and broad datasets of ExAC and gnomAd at similar frequencies: 0.00009 (11/121024 and 24/277022 chrs tested, respectively), predominantly in individuals of African descent (0.00068; 7/10210 and 13/24012 chrs tested). The latter frequency is similar to the expected allele frequency for a pathogenic variant in BRC2 gene (0.00075). The variant has been reported in several BrC patients without strong evidence for causality. In addition, multiple clinical labs classified this variant as VUS, and one lab classified it as likely benign, all without evidence for independent evaluation. Taking together, the variant was classified as VUS-Possibly Benign.
Invitae RCV000167806 SCV000072481 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-15 criteria provided, single submitter clinical testing
Pathway Genomics RCV000077333 SCV000223762 uncertain significance Breast-ovarian cancer, familial 2 2014-10-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000044468 SCV000600601 uncertain significance not specified 2016-09-23 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044468 SCV000587549 uncertain significance not specified 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077333 SCV000109130 uncertain significance Breast-ovarian cancer, familial 2 2007-07-09 no assertion criteria provided clinical testing

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