Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001704614 | SCV000569152 | likely benign | not provided | 2021-03-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001045245 | SCV001209083 | uncertain significance | Developmental and epileptic encephalopathy, 12 | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 14 of the PNKP gene. It does not directly change the encoded amino acid sequence of the PNKP protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs776617733, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PNKP-related conditions. ClinVar contains an entry for this variant (Variation ID: 420345). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002526571 | SCV003742077 | uncertain significance | Inborn genetic diseases | 2021-08-02 | criteria provided, single submitter | clinical testing | The c.1298+2_1298+5dupTAGC alteration is located in Intron 14 (E) of the PNKP gene. This alteration consists of a duplication of 4 nucleotides at nucleotide position c.12982 within Intron 14 (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |