Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000580527 | SCV000682312 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-07 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001853856 | SCV002271875 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-11-16 | 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. This variant disrupts the p.Ala2067 amino acid residue in ATM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22345219, 9887333, 25914063, 25077176). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 489567). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 2067 of the ATM protein (p.Ala2067Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. |