Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001954573 | SCV002191341 | pathogenic | Pigmentary pallidal degeneration | 2023-07-19 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 4 (c.1236-99_1259del) of the PANK2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PANK2 are known to be pathogenic (PMID: 11479594, 12510040). This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of pantothenate kinase-associated neurodegeneration (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1419098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |