Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480085 | SCV000570565 | likely pathogenic | not provided | 2020-10-20 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Illumina Laboratory Services, |
RCV000779581 | SCV000916260 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2018-10-15 | criteria provided, single submitter | clinical testing | This variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it 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. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. |
| Invitae | RCV000779581 | SCV001221960 | pathogenic | Hyperphosphatasia with intellectual disability syndrome 2 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg122*) in the PIGO gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIGO are known to be pathogenic (PMID: 22683086, 24417746). This variant is present in population databases (rs375682284, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with PIGO-related conditions. ClinVar contains an entry for this variant (Variation ID: 421377). For these reasons, this variant has been classified as Pathogenic. |