Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493352 | SCV000582799 | uncertain significance | not provided | 2017-05-16 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PIGO gene. The N162D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N162D variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N162D 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Centogene AG - |
RCV001809450 | SCV002059763 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2019-04-24 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001809450 | SCV002160393 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with aspartic acid at codon 162 of the PIGO protein (p.Asn162Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs776095449, ExAC 0.009%). This missense change has been observed in individual(s) with clinical features of PIGO-congenital disorder of glycosylation (Invitae). ClinVar contains an entry for this variant (Variation ID: 430076). 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: "Probably 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. |