ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.81-6T>C (rs80358179)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123287 SCV000166594 benign Hereditary breast and ovarian cancer syndrome 2017-11-07 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768652 SCV000219181 uncertain significance Breast and/or ovarian cancer 2015-12-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031284 SCV000296382 uncertain significance Breast-ovarian cancer, familial 1 2016-03-16 criteria provided, single submitter clinical testing
GeneDx RCV000423870 SCV000512276 benign not specified 2015-03-27 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.
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000123287 SCV000586862 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000423870 SCV000591237 uncertain significance not specified 2014-01-23 criteria provided, single submitter clinical testing
Color RCV000581130 SCV000683366 likely benign Hereditary cancer-predisposing syndrome 2015-03-11 criteria provided, single submitter clinical testing
Counsyl RCV000031284 SCV000785548 uncertain significance Breast-ovarian cancer, familial 1 2017-09-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000423870 SCV000916763 uncertain significance not specified 2018-11-13 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.81-6T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/5 computational tools predict no significant impact on normal splicing and a functional study supports these predictions reporting the variant as Class 1S, i.e., no effect on splicing (Leman_2018). The variant allele was found at a frequency of 4.1e-05 in 244486 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (4.1e-05 vs 0.001), allowing no conclusion about variant significance. c.81-6T>C has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Judkins_2005, Simard_2007, Spearman_2008). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.8537_8538delAG, p.Glu2846fsX22), providing supporting evidence for a benign role. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance (4x) or likely benign/benign (3x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Sharing Clinical Reports Project (SCRP) RCV000031284 SCV000053889 benign Breast-ovarian cancer, familial 1 2009-12-23 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031284 SCV000144228 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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