Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000799380 | SCV000939039 | likely pathogenic | Ataxia-telangiectasia syndrome | 2018-09-10 | criteria provided, single submitter | clinical testing | 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. Donor and acceptor splice site variants 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with ATM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 36 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Ambry Genetics | RCV002345779 | SCV002652716 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-09-18 | criteria provided, single submitter | clinical testing | The c.5496+2T>G intronic variant results from a T to G substitution two nucleotides after coding exon 35 in the ATM gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish 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). As such, this alteration is classified as likely pathogenic. |
| Myriad Genetics, |
RCV004027994 | SCV004933327 | likely pathogenic | Familial cancer of breast | 2024-01-25 | 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. |
| Baylor Genetics | RCV004027994 | SCV005055938 | likely pathogenic | Familial cancer of breast | 2024-03-18 | criteria provided, single submitter | clinical testing |