Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000464717 | SCV000563868 | pathogenic | Ataxia-telangiectasia syndrome | 2016-10-12 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 46- 63 of the ATM gene. The 5' boundary is likely confined to intron 45. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated ATM protein. While this particular variant has not been reported in the literature, gross deletions and truncating variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). This gross deletion eliminates the last 866 amino acid residues of the ATM protein, including the FAT, PI3/4 kinase, and FATC or PIK-related kinase domains, which are crucial for the proper function of the ATM protein (PMID: 23532176, 25460276, 23532176, 19781682, 23532176, 19781682). Also, a deletion encompassing exons 62-63 and the 3' UTR of ATM is reported as pathogenic and causative for autosomal recessive ataxia-telangiectasia (PMID: 9443866) and has been reported in an individual affected with breast cancer (Invitae database). For these reasons, this variant has been classified as Pathogenic. |