Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Childrens Diabetes Center, |
RCV000255740 | SCV000321298 | pathogenic | Mauriac syndrome | 2016-01-19 | criteria provided, single submitter | research | |
| Labcorp Genetics |
RCV002519869 | SCV003267630 | uncertain significance | Glycogen storage disease IXc | 2024-10-25 | 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 309 of the PHKG2 protein (p.Arg309Gln). This variant is present in population databases (rs572115942, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of glycogen storage disease (PMID: 27207549). ClinVar contains an entry for this variant (Variation ID: 253061). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects PHKG2 function (PMID: 27207549). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004767196 | SCV005381207 | uncertain significance | not specified | 2024-08-07 | criteria provided, single submitter | clinical testing | Variant summary: PHKG2 c.926G>A (p.Arg309Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-05 in 251014 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in PHKG2 causing Glycogen Phosphorylase Kinase Deficiency (8e-05 vs 0.0011), allowing no conclusion about variant significance. c.926G>A has been reported in the literature in a heterozygous individual affected with Mauriac disease (e.g. MacDonald_2016). This report does not provide unequivocal conclusions about association of the variant with Glycogen Phosphorylase Kinase Deficiency. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in reduced enzyme activity and partial inhibition of glycogen breakdown under low glucose conditions in vitro (e.g. MacDonald_2016). The following publication has been ascertained in the context of this evaluation (PMID: 27207549). ClinVar contains an entry for this variant (Variation ID: 253061). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV000239479 | SCV000297856 | uncertain significance | not provided | 2016-10-28 | no assertion criteria provided | literature only |