Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001851533 | SCV002262684 | likely pathogenic | Kufor-Rakeb syndrome; Autosomal recessive spastic paraplegia type 78 | 2023-03-14 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with clinical features of Kufor-Rakeb syndrome or hereditary spastic paraplegia (PMID: 17485642; Invitae). ClinVar contains an entry for this variant (Variation ID: 1221). 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 ATP13A2 protein function. Experimental studies have shown that this missense change affects ATP13A2 function (PMID: 22768177, 22847264, 23499937). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 504 of the ATP13A2 protein (p.Gly504Arg). |
| Mendelics | RCV000001280 | SCV002518548 | pathogenic | Kufor-Rakeb syndrome | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004766975 | SCV005380422 | likely pathogenic | Neurodegeneration with brain iron accumulation | 2024-08-22 | criteria provided, single submitter | clinical testing | Variant summary: ATP13A2 c.1510G>C (p.Gly504Arg) results in a non-conservative amino acid change located in the P-type ATPase, haloacid dehalogenase domain (IPR044492) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251098 control chromosomes (gnomAD). c.1510G>C has been reported in the literature in individuals affected with parkinsonism (Montaut_2018, Chien_2021). These data indicate that the variant is likely to be associated with disease. At least three publications reported experimental evidence evaluating an impact on protein function and this variant disrupted protein function (Covy_2012, Podhajska_2012, Matsui_2013). The following publications have been ascertained in the context of this evaluation (PMID: 34475127, 22847264, 23499937, 29913018, 22768177). ClinVar contains an entry for this variant (Variation ID: 1221). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000001280 | SCV000021430 | pathogenic | Kufor-Rakeb syndrome | 2007-05-08 | no assertion criteria provided | literature only | |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002251851 | SCV002523272 | uncertain significance | See cases | 2019-10-04 | flagged submission | clinical testing | ACMG classification criteria: PM2, PP3 |