Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000766326 | SCV000573212 | uncertain significance | not provided | 2017-02-16 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ARFGEF2 gene. The M1743T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M1743T 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 M1743T 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Genetic Services Laboratory, |
RCV000486863 | SCV000593312 | uncertain significance | not specified | 2016-05-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000766326 | SCV002972986 | uncertain significance | not provided | 2022-06-18 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1743 of the ARFGEF2 protein (p.Met1743Thr). This variant is present in population databases (rs367994107, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ARFGEF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 423506). 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 C25"). 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. |
Mayo Clinic Laboratories, |
RCV000766326 | SCV004225504 | uncertain significance | not provided | 2023-04-04 | criteria provided, single submitter | clinical testing |