Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000687478 | SCV000815045 | likely pathogenic | Ataxia-telangiectasia syndrome | 2023-02-14 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 5 of the ATM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer and/or lung cancer (PMID: 29625052, 31721094). ClinVar contains an entry for this variant (Variation ID: 567404). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Color Diagnostics, |
RCV001176630 | SCV001340666 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-05-25 | criteria provided, single submitter | clinical testing | This variant causes a G to C nucleotide substitution at the -1 position of intron 5 of the ATM gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has been reported in an individual affected with lung cancer (PMID: 31721094). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Myriad Genetics, |
RCV004026265 | SCV004932575 | likely pathogenic | Familial cancer of breast | 2024-03-12 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |