Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780878 | SCV000918504 | uncertain significance | not specified | 2017-11-20 | criteria provided, single submitter | clinical testing | Variant summary: The ATM c.2124+5G>A variant involves the alteration of a conserved intronic nucleotide and 5/5 splice prediction tools predict an effect on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 243872 control chromosomes (gnomAD). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
| Mendelics | RCV000988665 | SCV001138468 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000988665 | SCV001390905 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-06-15 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 633050). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 13 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. 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. 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. |