ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3082C>T (p.Arg1028Cys) (rs80357049)

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Total submissions: 10
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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) RCV000031087 SCV001161500 benign Breast-ovarian cancer, familial 1 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 = 0.000019
Invitae RCV000048066 SCV000076079 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000165900 SCV000216655 likely benign Hereditary cancer-predisposing syndrome 2019-02-28 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
GeneDx RCV000442663 SCV000526567 likely benign not specified 2016-10-31 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.
Color Health, Inc RCV000165900 SCV000688420 likely benign Hereditary cancer-predisposing syndrome 2017-10-24 criteria provided, single submitter clinical testing
Mendelics RCV000031087 SCV001140561 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000031087 SCV001287308 uncertain significance Breast-ovarian cancer, familial 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000442663 SCV001361790 uncertain significance not specified 2019-12-20 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3082C>T (p.Arg1028Cys) 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 2e-05 in 251110 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3082C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Klemp_2000, Coulet_2010, Azzollini_2016, Schenkel_2016) and endometrioid cancer (Garcia-Sanz_2016) without strong evidence for causality. These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. The variant has also been found as a homozygous variant in a patient with a history of chronic lymphatic leukemia and breast cancer, but who did not exhibit symptoms typical of Fanconi anemia, as would be expected in a homozygous patient if the variant were pathogenic (Bondavalli_2018). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar (evaluation after 2014) and cited the variant as likley benign (n=4) and uncertain significance (n=1) . Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Sharing Clinical Reports Project (SCRP) RCV000031087 SCV000053683 likely benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031087 SCV000144629 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing

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