ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3581G>A (p.Gly1194Asp) (rs28897721)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131681 SCV000186717 likely benign Hereditary cancer-predisposing syndrome 2017-08-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Biesecker Lab/Human Development Section,National Institutes of Health RCV000034439 SCV000043207 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000077309 SCV000146262 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735541 SCV000219329 likely benign Breast and/or ovarian cancer 2017-02-07 criteria provided, single submitter clinical testing
Color RCV000131681 SCV000902800 likely benign Hereditary cancer-predisposing syndrome 2015-11-08 criteria provided, single submitter clinical testing
Counsyl RCV000077309 SCV000487793 benign Breast-ovarian cancer, familial 2 2015-11-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000440462 SCV000591870 benign not specified 2012-09-05 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077309 SCV000244439 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 = 0.0000646
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735541 SCV000863679 uncertain significance Breast and/or ovarian cancer no assertion criteria provided clinical testing
GeneDx RCV000440462 SCV000518131 likely benign not specified 2017-08-15 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 RCV000440462 SCV000694707 likely benign not specified 2018-10-01 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3581G>A (p.Gly1194Asp) results in a non-conservative amino acid change located in the BRCA2 repeat region. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.3e-05 in 278020 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (8.3e-05 vs 0.00075), allowing no conclusion about variant significance. The variant, c.3581G>A, has been reported in the literature in individuals affected with Breast and Ovarian Cancer (e.g. Alsop 2012, Musolino 2007), without strong evidence for pathogenicity. The variant was predicted to be neutral with a multifactorial probability model, based on tumor pathology, clinical histories, family studies and co-occurrence with deleterious mutations (Easton 2007). In addition, UMD BRCA2 database classified this variant as 'likely neutral'. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (3x) / likely benign (3x). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000044227 SCV000072240 benign Hereditary breast and ovarian cancer syndrome 2017-12-24 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077309 SCV000109106 uncertain significance Breast-ovarian cancer, familial 2 2008-05-02 no assertion criteria provided clinical testing

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