Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004770209 | SCV005380855 | uncertain significance | not specified | 2024-08-08 | criteria provided, single submitter | clinical testing | Variant summary: AMPD2 c.970C>T (p.Arg324Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251294 control chromosomes. c.970C>T has been reported in the literature in a homozygous individual affected with Pontocerebellar Hypoplasia, Type 9 (Kortm_2018). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29463858). ClinVar contains an entry for this variant (Variation ID: 1332816). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Labcorp Genetics |
RCV002542417 | SCV003514985 | uncertain significance | Hereditary spastic paraplegia 63; Pontocerebellar hypoplasia type 9 | 2022-01-03 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs776868175, gnomAD 0.003%). This missense change has been observed in individual(s) with pontocerebellar hypoplasia (PMID: 29463858). 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 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. 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 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). |
| Kasturba Medical College, |
RCV001806390 | SCV002053951 | likely pathogenic | Pontocerebellar hypoplasia type 9 | criteria provided, single submitter | research |