ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.81-17C>G (rs757442952)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001087073 SCV000253521 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-11 criteria provided, single submitter clinical testing
Counsyl RCV000409501 SCV000488825 uncertain significance Breast-ovarian cancer, familial 1 2016-07-21 criteria provided, single submitter clinical testing
GeneDx RCV000441560 SCV000512275 likely benign not specified 2017-05-26 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 RCV000583744 SCV000688671 likely benign Hereditary cancer-predisposing syndrome 2017-10-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000441560 SCV000699309 benign not specified 2021-03-14 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.81-17C>G 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. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00011 in 244288 control chromosomes, predominantly at a frequency of 0.00078 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome (0.00011 vs 0.001), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.81-17C>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. At-least one co-occurrence with another pathogenic variant has been observed at our laboratory (MSH2 c.366+1G>A), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant on homology directed repair activity (example, Findlay_2018). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=5; VUS, n=1). Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics,PreventionGenetics RCV000589921 SCV000806986 likely benign not provided 2017-06-12 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000589921 SCV000591236 uncertain significance not provided no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000409501 SCV001243711 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.