Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000500375 | SCV000596488 | likely pathogenic | Microcephaly, seizures, and developmental delay | 2017-04-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001226527 | SCV001398844 | pathogenic | Developmental and epileptic encephalopathy, 12 | 2023-03-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects PNKP function (PMID: 27066567). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 190219). This variant has been observed in individual(s) with PNKP-related conditions (PMID: 25728773, 27066567, 30039206; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs786205207, gnomAD 0.05%). This variant, c.1221_1223del, results in the deletion of 1 amino acid(s) of the PNKP protein (p.Thr408del), but otherwise preserves the integrity of the reading frame. |
Institute of Medical Genetics and Applied Genomics, |
RCV001268911 | SCV001448160 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Laboratório de Neurologia Aplicada e Experimental, |
RCV001093540 | SCV001934609 | pathogenic | Charcot-Marie-Tooth disease type 2B2 | 2021-07-20 | criteria provided, single submitter | research | The variant p.Thr408Del variant in the PNKP gene has been observed in patients with CMT2B2 and ataxia with oculomotor apraxia type 4. ClinVar classifies this variant as Pathogenic (Variation ID: 190219), 2 stars (multiple consistent, 6 submissions), citing 3 articles (30039206, 27066567 and 25728773). This variant is present in heterozygous in 15 alleles in the GnomAD database and absents in the ABraOM database. This variant deletes one amino acid of the PNKP protein, which is highly conserved across different species. This variant is in an important functional domain of the protein (Kinase). In summary, the p.Thr408Del meets our criteria to be classified as pathogenic. |
OMIM | RCV000170438 | SCV000218380 | pathogenic | Ataxia - oculomotor apraxia type 4 | 2015-03-05 | no assertion criteria provided | literature only | |
Mendelics | RCV000170438 | SCV000222876 | pathogenic | Ataxia - oculomotor apraxia type 4 | 2015-04-09 | no assertion criteria provided | clinical testing | |
OMIM | RCV001093540 | SCV001250589 | pathogenic | Charcot-Marie-Tooth disease type 2B2 | 2015-03-05 | no assertion criteria provided | literature only |