Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001205809 | SCV001377084 | pathogenic | Ataxia-telangiectasia syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 20 of the ATM gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs192810283, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with ataxia-telangiectasia, breast cancer, and/or prostate cancer (PMID: 32853339, 35220195, 35260754). ClinVar contains an entry for this variant (Variation ID: 936903). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002319674 | SCV002606803 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-08 | criteria provided, single submitter | clinical testing | The c.3077+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 19 of the ATM gene. This nucleotide position is highly conserved in available vertebrate species. 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. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). As such, this alteration is classified as likely pathogenic. |
| Baylor Genetics | RCV003469332 | SCV004212238 | pathogenic | Familial cancer of breast | 2022-08-10 | criteria provided, single submitter | clinical testing | |
| Laboratory for Genotyping Development, |
RCV003163562 | SCV002758234 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |