Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481524 | SCV000574350 | uncertain significance | not provided | 2017-03-23 | criteria provided, single submitter | clinical testing | The G240D variant in the ACO2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G240D variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G240D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G240D as a variant of uncertain significance. |
| Labcorp Genetics |
RCV000481524 | SCV002962568 | uncertain significance | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ACO2 protein function. ClinVar contains an entry for this variant (Variation ID: 424533). This missense change has been observed in individual(s) with clinical features of autosomal recessive infantile cerebellar-retinal degeneration (PMID: 32519519). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs141878785, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 240 of the ACO2 protein (p.Gly240Asp). 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. |
| OMIM | RCV001255995 | SCV001432777 | pathogenic | Infantile cerebellar-retinal degeneration | 2020-09-16 | no assertion criteria provided | literature only |