ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1181A>C (p.Glu394Ala) (rs56016241)

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Total submissions: 12
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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) RCV000077252 SCV001161605 benign Breast-ovarian cancer, familial 2 2019-06-18 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 = 0.000915
Invitae RCV000043752 SCV000071765 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-19 criteria provided, single submitter clinical testing
GeneDx RCV000200974 SCV000210264 likely benign not specified 2017-08-07 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 RCV000165113 SCV000215823 likely benign Hereditary cancer-predisposing syndrome 2020-09-14 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign);No disease association in small case-control study
Counsyl RCV000077252 SCV000488146 uncertain significance Breast-ovarian cancer, familial 2 2016-02-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000200974 SCV000600472 uncertain significance not specified 2017-01-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000200974 SCV000694517 uncertain significance not specified 2019-04-15 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1181A>C (p.Glu394Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250208 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1181A>C has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Caux-Moncoutier_2011, Palomba_2009, Carney_2010, Miolo_2009, Apessos_2018). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A co-occurrence with a pathogenic variant has been reported (BIC database: BRCA2 c.8168A>G, p.Asp2723Gly), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant five times as uncertain significance and once as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Mendelics RCV000043752 SCV000838752 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000165113 SCV000910939 likely benign Hereditary cancer-predisposing syndrome 2016-08-18 criteria provided, single submitter clinical testing
Mendelics RCV000077252 SCV001138991 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077252 SCV000109049 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077252 SCV000145825 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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