ClinVar Miner

Submissions for variant NM_000294.3(PHKG2):c.454C>T (p.Arg152Ter)

dbSNP: rs772912966
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centogene AG - the Rare Disease Company RCV001250205 SCV001424474 likely pathogenic Glycogen storage disease type IXc criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003770291 SCV004611955 pathogenic Glycogen storage disease IXc 2023-01-30 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg152*) in the PHKG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHKG2 are known to be pathogenic (PMID: 8896567, 17689125, 21646031). This variant is present in population databases (rs772912966, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of PHKG2-related conditions (PMID: 31508908, 32697758). ClinVar contains an entry for this variant (Variation ID: 973563).
Neuberg Centre For Genomic Medicine, NCGM RCV003770291 SCV005690617 pathogenic Glycogen storage disease IXc 2023-06-22 criteria provided, single submitter clinical testing The observed stop gain c.454C>T (p.Arg152Ter) variant in PHKG2 gene has been previously reported in homozygous state in multiple individuals affected with Glycogen storage disease IXc (Waheed N et al. 2020; Kido J et al. 2021). The p.Arg152Ter variant is present with allele frequency of 0.0004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic. Computational evidence (Mutation Taster - Disease causing) predicts damaging effect on protein structure and function for this variant. The reference nucleotide change c.454C>T in PHKG2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. In the absence of another reportable variant in PHKG2 gene, the molecular diagnosis is not confirmed.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.