Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001190050 | SCV001357463 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-25 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001326146 | SCV001517160 | likely pathogenic | Ataxia-telangiectasia syndrome | 2023-07-10 | 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 not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 927042). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant 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. 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. |
Ambry Genetics | RCV001190050 | SCV002668424 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-11 | criteria provided, single submitter | clinical testing | The c.7307+2dupT intronic variant, results from a duplication of one nucleotide after coding exon 48 of the ATM gene. 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |