ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5467+2T>G

dbSNP: rs80358009
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001051199 SCV001215342 likely pathogenic Hereditary breast ovarian cancer syndrome 2019-06-19 criteria provided, single submitter clinical testing This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 125852). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the C-terminal end of the BRCA1 protein partially including the BRCT domain (residues 1646-1859), which is important for DNA repair activity (PMID: 11573086, 14576433, 15133503, 25652403). While functional studies have not been performed to directly test the effect on BRCA1 protein function, this suggests that disruption of this region of the protein may be causative of disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in the last intron (intron 22) of the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State RCV001051199 SCV002025896 likely pathogenic Hereditary breast ovarian cancer syndrome 2021-11-16 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112660 SCV000145523 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 1999-12-30 no assertion criteria provided clinical testing

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.