Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002396319 | SCV002670624 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-12-14 | criteria provided, single submitter | clinical testing | The c.7630-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 51 of the ATM gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and may result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Another alteration impacting the same acceptor site (c.7630-2A>C) has been shown to have a similar impact on splicing and has been detected in numerous individuals with ataxia telangiectasia and has been shown (Sandoval N et al. Hum. Mol. Genet. 1999 Jan;8:69-79; Teraoka S et al. Am J Hum Genet. 1999 Jun;64(6):1617-31; Coutinho G et al. Am. J. Med. Genet. A. 2004 Apr;126A:33-40; Soukupova J et al. Neuromolecular Med. 2011 Sep;13:204-11; Nespoli L et al. Case Reports Immunol, 2013 Oct;2013:296827; Podralska MJ et al. Mol Genet Genomic Med. 2014 Nov;2:504-11). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV004056482 | SCV004932059 | pathogenic | Familial cancer of breast | 2024-02-02 | criteria provided, single submitter | clinical testing | This variant is considered 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. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 9443866, 9887333, 10330348]. Functional studies indicate this variant impacts protein function [PMID: 9443866, 9887333, 10330348]. |