Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000631202 | SCV000752216 | pathogenic | Pigmentary pallidal degeneration | 2017-12-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe418Leufs*33) in the PANK2 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PANK2 are known to be pathogenic (PMID: 11479594, 12510040). This variant has not been reported in the literature in individuals with PANK2-related disease. This variant is not present in population databases (ExAC no frequency). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000631202 | SCV001448487 | likely pathogenic | Pigmentary pallidal degeneration | 2020-11-16 | criteria provided, single submitter | clinical testing | Variant summary: PANK2 c.1250_1251dupCT (p.Phe418LeufsX33) 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 patients affected with Pantothenate Kinase-Associated Neurodegeneration (HGMD). The variant was absent in 251444 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1250_1251dupCT in individuals affected with Pantothenate Kinase-Associated Neurodegeneration and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |