ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5022C>T (p.Ile1674=)

gnomAD frequency: 0.00001  dbSNP: rs786203868
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
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) RCV000495487 SCV000578465 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 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000167361 SCV000218213 likely benign Hereditary cancer-predisposing syndrome 2014-12-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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 RCV001640250 SCV000605899 likely benign not provided 2021-04-27 criteria provided, single submitter clinical testing
Invitae RCV000550800 SCV000636004 likely benign Hereditary breast ovarian cancer syndrome 2024-01-27 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000167361 SCV000683242 likely benign Hereditary cancer-predisposing syndrome 2016-06-13 criteria provided, single submitter clinical testing
Counsyl RCV000495487 SCV000785187 likely benign Breast-ovarian cancer, familial, susceptibility to, 1 2017-05-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000508616 SCV000916750 likely benign not specified 2019-08-21 criteria provided, single submitter clinical testing
GeneDx RCV001640250 SCV001856786 benign not provided 2015-04-23 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000495487 SCV004016786 likely benign Breast-ovarian cancer, familial, susceptibility to, 1 2023-07-07 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003491918 SCV004240274 uncertain significance Breast and/or ovarian cancer 2022-10-17 criteria provided, single submitter clinical testing
King Laboratory, University of Washington RCV001171418 SCV001251323 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1; Hereditary breast ovarian cancer syndrome 2019-09-01 no assertion criteria provided research
University of Washington Department of Laboratory Medicine, University of Washington RCV000495487 SCV002568356 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2021-07-21 no assertion criteria provided clinical testing Based on functional RNA studies, the BRCA1 c.5022C>T variant was shown to disrupt splicing regulatory motifs in BRCA1 exon 17 and results in exon skipping, which leads to a premature stop codon in 32% of transcripts from the variant allele (Casadei 2019). These studies provide some evidence that this variant is pathogenic for a hypomorphic risk. Because this variant results in some full length BRCA1 transcripts, the cancer risks conferred by this variant are likely to be different than the risks associated with other pathogenic BRCA1 variants. Some literature suggests that variants like this one should be classified as variants of uncertain significance because the level of associated risk has not been established (Fraile-Bethencourt 2017).

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.