Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001040379 | SCV001203950 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-03-27 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 27 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein, but it affects a nucleotide within the consensus splice site of the intron. |
| Ambry Genetics | RCV002320248 | SCV002630637 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-24 | criteria provided, single submitter | clinical testing | The c.4109+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 26 in 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. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Gene |
RCV003223691 | SCV003919591 | likely pathogenic | not provided | 2022-10-18 | criteria provided, single submitter | clinical testing | Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28126470) |
| Fulgent Genetics, |
RCV005049738 | SCV005681279 | likely pathogenic | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2024-03-30 | criteria provided, single submitter | clinical testing |