PGAM2 G97D - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

PGAM2 G97D

(PGAM2 Gly97Asp)


Short summary

This variant was implicated in a dominant fashion for causing Phosphoglycerate Mutase Deficiency in single Japanese family but had conflicting evidence — two heterozygotes were asymptomatic. This is labeled as dominant, but disease-causing mutations in this gene are generally recessive.

Variant evidence
Computational 4

NBLOSUM=3, disease associated gene, conserved site, secondary structure affected.

See Hadjigeorgiou GM et al. 1999 (10545043).

Functional -
Case/Control 2

significance = 0.047, high OR.

See Hadjigeorgiou GM et al. 1999 (10545043), unpublished research (below).

Familial

Segregation in one family but with conflicting evidence — two potentially asymptomatic.

See Hadjigeorgiou GM et al. 1999 (10545043), unpublished research (below).

 
Clinical importance
Severity 2

Exercise intolerance

See unpublished research (below).

Treatability 3

Lifestyle changes can help

See unpublished research (below).

Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

dominant

Summary of published research, and additional commentary

 

Total cases/controls case+ case– control+ control– p-value odds ratio
Phosphoglycerate Mutase Deficiency
1 0 0 20 0.0476

 

Allele frequency

  • T @ chr7:44071363: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 0.8% (1/128)

Publications
 

Hadjigeorgiou GM, Kawashima N, Bruno C, Andreu AL, Sue CM, Rigden DJ, Kawashima A, Shanske S, DiMauro S. Manifesting heterozygotes in a Japanese family with a novel mutation in the muscle-specific phosphoglycerate mutase (PGAM-M) gene. Neuromuscul Disord. 1999 Oct;9(6-7):399-402. PubMed PMID: 10545043.

This variant was found in 2 Japanese individuals (the proband (55yo) and his son (22yo)) in a heterozygous manner with glycogen storage disease X and exercise intolerance. The variant was also present in a 19yo son and 18yo daughter who are currently asymptomatic. It was not seen in 20 ethnically matched controls. The authors conclude pathogenecity in this family due to evolutionary conservation, no other mutations present, no other biochemical defect detected, not in controls and a predicted strain on the secondary structure sufficient to alter the active site. Most variants in the gene are recessive, but manifesting heterozygosity has been noted.

Cases/controls case+ case– control+ control– p-value odds ratio
Phosphoglycerate Mutase Deficiency
1 0 0 20 0.0476

 

Genomes
 

GS18555 - var-GS18555-1100-36-ASM
het T @ chr7:44071364

 

NA18555

 

show discussion

Discussion

This area of NA1855’s genome has been re-sequenced and the variant has been re-confirmed to be a heterozygous T.

Other external references
 

    PolyPhen-2
  • Score: 0.996 (probably damaging)
    Web search results (3 hits -- see all)
  • Mendelian Inheritance in Man Document Reader
    Two family members heterozygous for the G97D mutation presented with exercise intolerance and muscle cramps. ... specific phosphoglycerate mutase, PGAM2, mapped to chromosome 7 ...
    www.angis.org.au/bin/Databases/BIRX/birx_doc?phtomim+261670
  • PGAM1 - phosphoglycerate mutase 1 (brain)
    This assignment shows that the PGAM2 is not syntenic with the nonmuscle form of PGAM1 (B) which has been ... of a highly conserved glycine at codon 97 with aspartic acid (G97D) ...
    www.ihop-net.org/UniPub/iHOP/bng/90969.html

Other in silico analyses
 

  • NBLOSUM100 score = 4
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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