Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000004810 | SCV002305227 | pathogenic | Pigmentary pallidal degeneration | 2023-09-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg264 amino acid residue in PANK2. Other variant(s) that disrupt this residue have been observed in individuals with PANK2-related conditions (PMID: 16437574, 33098801), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt PANK2 protein function. ClinVar contains an entry for this variant (Variation ID: 4550). This variant is also known as p.R154W . This missense change has been observed in individuals with pantothenate kinase-associated neurodegeneration (PMID: 11479594, 16437574, 22221393). This variant is present in population databases (rs137852961, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 264 of the PANK2 protein (p.Arg264Trp). |
| Gene |
RCV002460885 | SCV002757691 | likely pathogenic | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing | Observed multiple times with a second PANK2 variant in unrelated patients with PANK2-related neurodegeneration in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in all cases (Darling et al., 2017; Hartig et al., 2006; Zhou et al., 2001); Published functional studies demonstrate that the variant results in a significant decrease in PANK2 protein activity (Hong et al., 2007; Zhang et al., 2006); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31540697, 27544236, 32928263, 28456385, 22221393, 11479594, 32456086, 16272150, 16437574, 28845923, 17631502) |
| Fulgent Genetics, |
RCV000004810 | SCV005661852 | likely pathogenic | Pigmentary pallidal degeneration | 2024-06-07 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004810 | SCV005887919 | pathogenic | Pigmentary pallidal degeneration | 2025-01-08 | criteria provided, single submitter | clinical testing | Variant summary: PANK2 c.790C>T (p.Arg264Trp)/c.460C>T (p.Arg154Trp) 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 8e-06 in 251420 control chromosomes (gnomAD). c.790C>T has been reported in the literature in multiple individuals affected with Pantothenate Kinase-Associated Neurodegeneration (e.g. Zhou_2001, Leoni_2012). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 11479594, 22221393). ClinVar contains an entry for this variant (Variation ID: 4550). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000004810 | SCV000024986 | pathogenic | Pigmentary pallidal degeneration | 2001-08-01 | no assertion criteria provided | literature only |