ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8525G>A (p.Arg2842His) (rs80359105)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077444 SCV000244486 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 = 0.000259
Invitae RCV000587725 SCV000073558 benign not provided 2019-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000045545 SCV000210671 likely benign not specified 2017-11-17 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.
Ambry Genetics RCV000163013 SCV000213501 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Counsyl RCV000077444 SCV000487766 benign Breast-ovarian cancer, familial 2 2015-12-04 criteria provided, single submitter clinical testing
Color RCV000163013 SCV000537493 likely benign Hereditary cancer-predisposing syndrome 2015-08-14 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000045545 SCV000588120 benign not specified 2017-04-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587725 SCV000695163 likely benign not provided 2016-04-08 criteria provided, single submitter clinical testing Variant summary: The c.8525G>A variant affects a conserved nucleotide, resulting in amino acid change from Arg to His. 5/5 in-silico tools predict damaging outcome for this variant; however, they are not definitive. This variant is found in 7/121316 control chromosomes predominantly in East Asian population with an allele frequency of 0.00057 (5/8634 chromosomes) which does not exceed the maximal expected frequency of a pathogenic allele (0.0007503) in this gene. However, the frequency data may still suggest that this variant is a rare polymorphism. The variant has been reported in multiple HBOC patients/families without strong evidence for causality. More importantly, the variant has been reported to co-occur with truncating variants in BRCA1/2, namely BRCA1 p.Glu879Ter and BRCA2 p.Gln3066Ter, strongly suggesting for benign outcome. Multifactorial probability based models also strongly suggest for a benign outcome. Multiple clinical labs and reputable databases have classified this variant as benign/likely benign. Taken together, this variant has been classified as likely benign.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077444 SCV000743348 likely benign Breast-ovarian cancer, familial 2 2017-07-28 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077444 SCV000744541 benign Breast-ovarian cancer, familial 2 2017-05-31 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077444 SCV000109242 benign Breast-ovarian cancer, familial 2 2010-10-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077444 SCV000147391 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077444 SCV000733318 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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