Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002266168 | SCV002547705 | pathogenic | Pigmentary pallidal degeneration | 2022-05-16 | criteria provided, single submitter | clinical testing | Variant summary: PANK2 c.994C>T (p.Gln332X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been reported in association with Pantothenate Kinase-Associated Neurodegeneration in the HGMD database. The variant was absent in 251250 control chromosomes. c.994C>T has been reported in the literature as a homozygous genotype in multiple individuals affected with Pantothenate Kinase-Associated Neurodegeneration (example, Hartig_2006, Akcakaya_2017, Chang_2020). These data indicate that the variant is very likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV002266168 | SCV003443357 | pathogenic | Pigmentary pallidal degeneration | 2022-07-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with pantothenate kinase-associated neurodegeneration (PMID: 28113101). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln332*) in the PANK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PANK2 are known to be pathogenic (PMID: 11479594, 12510040). |