Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001031916 | SCV001195223 | pathogenic | Ataxia-telangiectasia syndrome | 2019-05-09 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 62-63 of the ATM gene. The 5' boundary is likely confined to intron 61. 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 is not anticipated to result in nonsense mediated decay, it is expected to delete the last 106 amino acids of the ATM protein. Deletions encompassing exons 62-63 of ATM have been reported in several individuals with ataxia-telangiectasia, some of whom were homozygous for this variant (PMID: 9443866, 9792409,25614872). In addition, this variant has been observed in individuals with breast cancer (PMID: 25428789, 26681312). This variant is also known as a deletion of exons 64-65 in the literature. A missense change in exon 63 (p.Arg3008Cys) and a deletion encompassing exon 63 have been determined to be pathogenic (PMID: 9872980, 12552566, 23807571). This suggests that exon 63 is critical for ATM protein function. For these reasons, this deletion has been classified as Pathogenic. |