Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000147129 | SCV000194489 | uncertain significance | Microcephalic osteodysplastic primordial dwarfism type II | 2014-04-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000522969 | SCV000619888 | uncertain significance | not provided | 2017-08-11 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PCNT gene. The S2433P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S2433P variant is observed in 6/10382 (0.1%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S2433P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant likely does not alter 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 | RCV000522969 | SCV002112116 | uncertain significance | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 149 of the PCNT protein (p.Ser149Cys). This variant is present in population databases (rs111737555, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with PCNT-related conditions. ClinVar contains an entry for this variant (Variation ID: 159604). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Prevention |
RCV003398789 | SCV004103420 | likely benign | PCNT-related condition | 2024-01-29 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |