Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002988515 | SCV003290446 | likely pathogenic | Ataxia-telangiectasia syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 49 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with ataxia-telangiectasia (PMID: 35221880). ClinVar contains an entry for this variant (Variation ID: 2078215). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 35221880; Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |