POLG2 G416A - GET-Evidence

Curation:
Currentness:

POLG2 G416A

(POLG2 Gly416Ala)


Short summary

Rare but presumed benign. It was believed to be non-causal in a patient with a different mutation, and functional analysis found no difference from wild type.

Variant evidence
Computational -
Functional 1

No difference from wild type

See Ferraris S et al. 2008 (18195150).

Case/Control 1

Coincidentally found in a patient where another causal variant implicated, implying it is a rare nonpathogenic polymorphism

See Ferraris S et al. 2008 (18195150).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr17:62476451: 1.2% (128/10754) in EVS
  • G @ chr17:59906912: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 1.2% (128/10754)

Publications
 

Ferraris S, Clark S, Garelli E, Davidzon G, Moore SA, Kardon RH, Bienstock RJ, Longley MJ, Mancuso M, Gutiérrez Ríos P, Hirano M, Copeland WC, DiMauro S. Progressive external ophthalmoplegia and vision and hearing loss in a patient with mutations in POLG2 and OPA1. Arch Neurol. 2008 Jan;65(1):125-31. PubMed PMID: 18195150; PubMed Central PMCID: PMC2364721.

This variant was seen heterozygously in a patient with combination of symptoms: chronic progressive external ophthalmoplegia, hearing loss, vision loss, anemia, and hypogonadism. The authors functionally characterized the POLG2 variant and found no difference from wild type. Because of this, they looked for another variant and found one in OPA1, which they concluded was more likely the causal variant.

Genomes
 

Other external references
 

    dbSNP
  • rs17850455
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.999 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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