Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480492 | SCV000565373 | likely pathogenic | not provided | 2016-06-15 | criteria provided, single submitter | clinical testing | The P197L variant in the PIGO gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The P197L variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P197L 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 moderately conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P197L as a likely pathogenic variant. |
| Mendelics | RCV000988182 | SCV001137813 | likely pathogenic | Hyperphosphatasia with intellectual disability syndrome 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000988182 | SCV001331085 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV000988182 | SCV002184296 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2022-05-04 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 197 of the PIGO protein (p.Pro197Leu). This variant is present in population databases (rs150734953, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of PIGO-related conditions (PMID: 26633542). ClinVar contains an entry for this variant (Variation ID: 418409). 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV000988182 | SCV003807019 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2023-02-02 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4 supporting, PM2 moderated, BP4 supporting |