Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000147357 | SCV000194732 | uncertain significance | Microcephaly, seizures, and developmental delay | 2013-08-05 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000178285 | SCV000230338 | uncertain significance | not provided | 2015-02-17 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000178285 | SCV001151999 | uncertain significance | not provided | 2018-12-01 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
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, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |