ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5406A>C (p.Thr1802=)

dbSNP: rs879255493
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000238914 SCV000578330 likely benign Breast-ovarian cancer, familial, susceptibility to, 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.04; http://priors.hci.utah.edu/PRIORS/).
GeneDx RCV000758844 SCV000525823 likely benign not provided 2018-06-07 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30209399)
Labcorp Genetics (formerly Invitae), Labcorp RCV000530982 SCV000636037 likely benign Hereditary breast ovarian cancer syndrome 2023-10-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575634 SCV000660976 likely benign Hereditary cancer-predisposing syndrome 2018-05-10 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758844 SCV000887727 likely benign not provided 2017-11-22 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000575634 SCV000904896 likely benign Hereditary cancer-predisposing syndrome 2018-03-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002229697 SCV002511775 likely benign not specified 2022-04-18 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5406A>C (p.Thr1802Thr) 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. The variant was absent in 251420 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5406A>C in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome has been reported. An in vitro study that assessed the effect of the variant in a haploid human cell line whose survival is dependent on intact BRCA1 function, demonstrated no damaging effect of this variant (Findlay 2018). Six submitters, including an expert panel (ENIGMA), have provided clinical-significance assessments for this variant in ClinVar after 2014, and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Fulgent Genetics, Fulgent Genetics RCV002494687 SCV002804225 likely benign Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S 2022-05-16 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000238914 SCV004817552 likely benign Breast-ovarian cancer, familial, susceptibility to, 1 2023-03-04 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000238914 SCV000297490 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2011-06-09 no assertion criteria provided clinical testing
Brotman Baty Institute, University of Washington RCV000238914 SCV001242710 not provided Breast-ovarian cancer, familial, susceptibility to, 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.