Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000555048 | SCV000622330 | pathogenic | Ataxia-telangiectasia syndrome | 2023-04-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 16 (also known as exon 18), but is expected to preserve the integrity of the reading-frame (PMID: 10330348). ClinVar contains an entry for this variant (Variation ID: 453414). Disruption of this splice site has been observed in individual(s) with clinical features of ataxia-telangiectasia (PMID: 10330348; Invitae). This sequence change affects a donor splice site in intron 16 of the ATM gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. |
| Ambry Genetics | RCV002431495 | SCV002731670 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-26 | criteria provided, single submitter | clinical testing | The c.2466+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 15 of the ATM gene. This alteration was reported in a patient with a clinical diagnosis of ataxia-telangiectasia (A-T) with second mutation not identified (Teraoka SN et al. Am. J. Hum. Genet., 1999 Jun;64:1617-31). In addition, another alteration impacting the same donor site (c.2466+1delG) has been described in an individual with A-T in conjunctions with another pathogenic ATM mutation (Cavalieri S, Ann. Hum. Genet. 2008 Jan; 72(Pt 1):10-8). This variant is also known as IVS18+1G>A in the literature This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Baylor Genetics | RCV003476226 | SCV004203872 | pathogenic | Familial cancer of breast | 2023-10-27 | criteria provided, single submitter | clinical testing |