Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000081505 | SCV000113436 | likely benign | not specified | 2017-09-29 | criteria provided, single submitter | clinical testing | |
| Genetic Services Laboratory, |
RCV000147348 | SCV000194723 | uncertain significance | Microcephaly, seizures, and developmental delay | 2013-11-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000081505 | SCV000514222 | uncertain significance | not specified | 2017-06-21 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PNKP gene. The R462Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R462Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. A different missense variant at the same position (R462P) has been reported in Human Gene Mutation Database in association with a PNKP-related disorder (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, the R462Q variant is observed in 17/514 (3.3%) alleles from individuals of Latino background in the ExAC dataset, which is greater than expected for this disorder (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001081069 | SCV000560523 | benign | Developmental and epileptic encephalopathy, 12 | 2024-01-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002313782 | SCV000847733 | likely benign | Inborn genetic diseases | 2018-07-10 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Athena Diagnostics | RCV000466734 | SCV001145115 | benign | not provided | 2018-10-16 | criteria provided, single submitter | clinical testing |