Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000258271 | SCV000326147 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002345344 | SCV002645958 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | The c.5075-8T>G intronic variant results from a T to G substitution 8 nucleotides upstream from coding exon 16 in the BRCA1 gene. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Another functional study utilizing a LCL with puromycin assay found that this alteration caused a complete splicing defect (Houdayer C et al. Hum Mutat, 2012 Aug;33:1228-38). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Brotman Baty Institute, |
RCV000258271 | SCV001242064 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |