Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Kasturba Medical College, |
RCV001806390 | SCV002053951 | likely pathogenic | Pontocerebellar hypoplasia type 9 | criteria provided, single submitter | research | ||
Invitae | RCV002542417 | SCV003514985 | uncertain significance | Hereditary spastic paraplegia 63; Pontocerebellar hypoplasia type 9 | 2022-01-03 | 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.Arg378 amino acid residue in AMPD2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29463858; Invitae). 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 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: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with pontocerebellar hypoplasia (PMID: 29463858). This variant is present in population databases (rs776868175, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 378 of the AMPD2 protein (p.Arg378Trp). |