Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001312531 | SCV001502987 | pathogenic | Glycogen storage disease IXa1 | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2 of the PHKA2 protein (p.Arg2Gly). This variant is present in population databases (rs140014925, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of glycogen storage disease type IXa (PMID: 34117828). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1013871). 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 expected to disrupt PHKA2 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001312531 | SCV001525913 | uncertain significance | Glycogen storage disease IXa1 | 2018-06-09 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Ce |
RCV002264263 | SCV002546150 | pathogenic | not provided | 2022-07-01 | criteria provided, single submitter | clinical testing | PHKA2: PP1:Strong, PM2, PS4:Moderate, PP3, PS3:Supporting |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230658 | SCV003928919 | pathogenic | Glycogen phosphorylase kinase deficiency | 2023-04-12 | criteria provided, single submitter | clinical testing | Variant summary: PHKA2 c.4C>G (p.Arg2Gly) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 182789 control chromosomes. c.4C>G has been reported in the literature in multiple individuals from multiple families affected with Glycogen Phosphorylase Kinase Deficiency (Benner_2021), and shown to segregate with disease. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified as Pathogenic (n=2) and VUS (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Institute of Human Genetics, |
RCV001312531 | SCV004100800 | likely pathogenic | Glycogen storage disease IXa1 | 2023-10-30 | criteria provided, single submitter | clinical testing | Criteria applied: PP1_STR,PS4_MOD,PM2_SUP,PP3 |