ClinVar Miner

Submissions for variant NM_000290.4(PGAM2):c.233G>A (p.Trp78Ter) (rs10250779)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000493394 SCV000224186 pathogenic not provided 2014-12-29 criteria provided, single submitter clinical testing
GeneDx RCV000493394 SCV000582131 pathogenic not provided 2021-06-20 criteria provided, single submitter clinical testing The most common pathogenic variant identified in patients of African ancestry with PGAM deficiency, likely due to a founder effect (Koo et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 8447317, 23169535, 27612597, 28944235, 19783439, 28492532, 6308514, 2987758, 27535533, 31589614)
Mayo Clinic Laboratories, Mayo Clinic RCV000493394 SCV000801666 pathogenic not provided 2020-02-04 criteria provided, single submitter clinical testing PVS1, PS4, PP4
Invitae RCV000000446 SCV000823057 pathogenic Glycogen storage disease type X 2019-10-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp78*) in the PGAM2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs10250779, ExAC 0.8%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals with phosphoglycerate mutase deficiency (PMID: 8447317, 27612597). ClinVar contains an entry for this variant (Variation ID: 418). Loss-of-function variants in PGAM2 are known to be pathogenic (PMID: 8447317, 19273759). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000446 SCV000020595 pathogenic Glycogen storage disease type X 1993-03-01 no assertion criteria provided literature only
Reproductive Health Research and Development,BGI Genomics RCV000000446 SCV001142367 pathogenic Glycogen storage disease type X 2020-01-06 no assertion criteria provided curation NM_000290.3:c.233G>A in the PGAM2 gene has an allele frequency of 0.007 in African subpopulation in the gnomAD database. Koo B et al. found compound heterozygous variants: c.233G>A, and c.278G>A in a patient with Phosphoglycerate mutase deficiency (PMID: 27612597). In addition, Tsujino S et al. found that three patients with phosphoglycerate mutase (PGAM) deficiency were homozygous for this nonsense variant (PMID: 8447317 ). The c.233G>A (p.Trp78*) variant in the PGAM2 gene results in a premature termination codon, predicted to cause a truncated or absent protein due to nonsense mediated decay. Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PVS1; PM3; PP4.

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