Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000808102 | SCV000948194 | likely pathogenic | Pigmentary pallidal degeneration | 2018-08-03 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants 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 has not been reported in the literature in individuals with PANK2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 4 of the PANK2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Division Of Personalized Genomic Medicine, |
RCV000808102 | SCV004190148 | likely pathogenic | Pigmentary pallidal degeneration | 2020-02-13 | criteria provided, single submitter | clinical testing | The c.1412+1G>C variant in the PANK2 gene is a homozgyous canonical splice site variant, which results in a single base pair substitution in intron 4 of 6 (NM_153638.3). Canonical splice site variants are precited to result in a null effect; however, this impact on protein has not been confirmed through functional studies. Loss-of-function variants in PANK2 have been established to be pathogenic (PMID: 12510040). This variant is absent in the Genome Aggregation Database (gnomAD), indicating it is not a common benign variant in the populations represented in this database. To the best of our knowledge, this specific variant has not been described in the literature to be associated with disease. However, it has been classified by another laboratory as likely pathogenic in the ClinVar database (Variant ID: 652533). |