ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1385A>G (p.Glu462Gly) (rs56403624)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162999 SCV000213487 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031319 SCV000145862 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162999 SCV000683419 likely benign Hereditary cancer-predisposing syndrome 2015-02-05 criteria provided, single submitter clinical testing
Counsyl RCV000031319 SCV000220497 likely benign Breast-ovarian cancer, familial 2 2014-07-10 criteria provided, single submitter literature only
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031319 SCV000744410 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000173630 SCV000591741 benign not specified 2013-11-18 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000173630 SCV000224758 benign not specified 2014-10-13 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031319 SCV000244421 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000293
GeneDx RCV000173630 SCV000210559 likely benign not specified 2018-03-05 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000031319 SCV000743259 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000195299 SCV000494425 benign Hereditary breast and ovarian cancer syndrome 2015-08-20 criteria provided, single submitter clinical testing Variant Summary: The c.1385A>G variant involves the alteration of a non-conserved nucleotide and 2/5 in silico tools predict a benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.023%, primarily observed in the European (Non-Finnish) cohort at a frequency of 0.041%. These frequencies do not exceed the maximal expected allele frequency for a pathogenic variant in BRCA2 (0.075%). The variant was reported in the literature and databases in individuals who also have pathogenic BRCA1 (n=1) and BRCA2 (n=3) mutations (UMD, BIC, Simard_2007) suggesting a benign nature of the variant. Additionally, the variant was found to not segregate with disease in families tested (3 affected family members did not carry the variant; Gomez Garcia_2009). Functional studies showed the variant performed similarly to wild-type BRCA2 in assays of cellular survival and viability, homologous recombination repair, and genome instability (Wu_2005). Multiple reputable databases and clinical labs all classify the variant as benign/likely benign (Emory Genteics, UMD, ARUP, Ambry Genetics, SCRP, GeneDx, Counsyl) along with publications using multifactorial probability based models (Lindor_2012, Gomez Garcia_2009). All data, including co-segregation, functional assays, co-occurrence and the occurrence of this variant in the control population all support the classification of benign, therefore this variant has been classified as benign.
Invitae RCV000195299 SCV000071806 benign Hereditary breast and ovarian cancer syndrome 2018-01-09 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000173630 SCV000538483 uncertain significance not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Multiple publications classify as VUS/not pathogenic; ExAC: 27/66408 European chromosomes
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656588 SCV000778645 benign not provided 2017-04-14 no assertion criteria provided clinical testing
PreventionGenetics RCV000173630 SCV000301756 likely benign not specified criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031319 SCV000053924 benign Breast-ovarian cancer, familial 2 2006-09-07 no assertion criteria provided clinical testing
Vantari Genetics RCV000162999 SCV000267014 benign Hereditary cancer-predisposing syndrome 2016-01-06 criteria provided, single submitter clinical testing

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