Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000561892 | SCV000660881 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-10 | criteria provided, single submitter | clinical testing | The c.2002-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 11 of the BARD1 gene. This nucleotide position is highly conserved in available vertebrate species. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. 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. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay; however, direct evidence for this alteration is unavailable. RNA studies have demonstrated that other alterations at this canonical splice site result in a transcript predicted to lead to a protein with an in-frame deletion of three amino acids; however, the exact functional impact of the deleted amino acids is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Myriad Genetics, |
RCV003335476 | SCV004044935 | likely pathogenic | Familial cancer of breast | 2023-05-25 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |