Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000634554 | SCV000755874 | uncertain significance | Glycogen storage disease type X | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 40 of the PGAM2 protein (p.Arg40Gln). This variant is present in population databases (rs140545494, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PGAM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 529224). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PGAM2 protein function with a negative predictive value of 80%. 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. |
| Illumina Laboratory Services, |
RCV000634554 | SCV001322019 | uncertain significance | Glycogen storage disease type X | 2018-01-12 | 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. |
| Gene |
RCV001569652 | SCV001793773 | likely benign | not provided | 2020-09-15 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27195159) |
| Ce |
RCV001569652 | SCV004185433 | likely benign | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | PGAM2: BP4 |
| Pittsburgh Clinical Genomics Laboratory, |
RCV000634554 | SCV005397245 | uncertain significance | Glycogen storage disease type X | 2022-06-03 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (G>A) at coding position 119 of the PGAM2 gene that results in an arginine to glutamine amino acid change at residue 40 of the PGAM2 protein. This is a previously reported variant (ClinVar) that has not been observed in the literature in individuals with PGAM2-related disease, to our knowledge. This sequence variant is present in control population datasets (gnomAD database 70/282798 alleles or 0.025%). Multiple bioinformatic tools predict that this variant would be tolerated, and the Arg40 residue is well conserved among the mammalian species examined. Functiol studies testing the effect of this variant on protein structure or activity have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this to be a variant of uncertain significance. ACMG Criteria: BP4, PM2 |