ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.1221_1223del (p.Thr408del)

dbSNP: rs786205207
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago 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, University Hospital Tübingen RCV001268911 SCV001448160 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Laboratório de Neurologia Aplicada e Experimental, Faculdade de Medicina de Ribeirao Preto – Universidade de Sao Paulo 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.