Submissions for variant NM_000290.4(PGAM2):c.533del (p.Gly178fs)

dbSNP: rs747947171

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000714736	SCV000845464	likely pathogenic	Glycogen storage disease type X	2018-08-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001570366	SCV001794650	likely pathogenic	not provided	2019-04-15	criteria provided, single submitter	clinical testing	Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 76 amino acids are lost and replaced with 30 incorrect amino acids; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31589614, 30310767, 29382405)
Invitae	RCV000714736	SCV003439535	pathogenic	Glycogen storage disease type X	2023-08-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly178Alafs*31) in the PGAM2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 76 amino acid(s) of the PGAM2 protein. This variant is present in population databases (rs747947171, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of glycogen storage disease (PMID: 19783439, 30310767). This variant is also known as 19783439, 33727708. ClinVar contains an entry for this variant (Variation ID: 587530). This variant disrupts a region of the PGAM2 protein in which other variant(s) (p.Met230Hisfs*6) have been observed in individuals with PGAM2-related conditions (PMID: 34237446). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.