ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.302C>T (p.Pro101Leu)

dbSNP: rs587784367
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147357 SCV000194732 uncertain significance Microcephaly, seizures, and developmental delay 2013-08-05 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000178285 SCV000230338 uncertain significance not provided 2015-02-17 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000178285 SCV001151999 uncertain significance not provided 2018-12-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000147357 SCV001449047 likely pathogenic Microcephaly, seizures, and developmental delay 2020-12-08 criteria provided, single submitter clinical testing This variant has been identified compound heterozygous with the variant NM_007254.3:c.498G>A, r.199_498del, p.Leu67_Lys166del in two fetuses with microcephaly, aplasia/hypoplasia of the cerebrum and cerebellum (hypoplastic frontal lobes, no corpus callosum) and facial dysmorphism (retrognathia, hypertelorism, long philtrum). The variant is maternally inherited. This missense variant c.302C>T, p.(Pro101Leu) in exon 4 of PNKP has been reported in ClinVar (ID 159793). The variant is absent from the general population (gnomAD). Multiple in silico-tools predict this variant as damaging. The variant is located in the FHA-domain. Taken together, we classify this variant as likely pathogenic based on the ACMG recommendations (Richards et al., 2015, PMID 25741868; criteria: PS4_MOD;PM1_SUP;PM2_SUP;PM3;PP3).
Ambry Genetics RCV002433634 SCV002754336 uncertain significance Inborn genetic diseases 2020-03-18 criteria provided, single submitter clinical testing The p.P101L variant (also known as c.302C>T), located in coding exon 3 of the PNKP gene, results from a C to T substitution at nucleotide position 302. The proline at codon 101 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.