Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001975059 | SCV002244435 | pathogenic | Pigmentary pallidal degeneration | 2023-05-25 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 2 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). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1458749). This variant is also known as IVS2-1G>C. Disruption of this splice site has been observed in individuals with clinical features of pantothenate kinase-associated neurodegeneration (PKAN) (PMID: 22221393, 27815806, 31088771). This variant is not present in population databases (gnomAD no frequency). |