WDR36 H212P - GET-Evidence

Curation:
Currentness:

WDR36 H212P

(WDR36 His212Pro)


Short summary

Probably benign.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect, other variants in this gene are associated with glaucoma

Functional 1

Functional study in yeast found no growth defect

See Footz TK et al. 2009 (19150991).

Case/Control 3

High frequency in controls supports no pathogenic effect

See Pasutto F et al. 2008 (18172102).

Familial

No familial data

 
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

  • C @ chr5:110436345: 0.0% (5/10734) in EVS
  • CC @ chr5:110464243: 0.9% (1/116) in GET-Evidence
  • Frequency shown in summary reports: 0.0% (5/10734)

Publications
 

Pasutto F, Mardin CY, Michels-Rautenstrauss K, Weber BH, Sticht H, Chavarria-Soley G, Rautenstrauss B, Kruse F, Reis A. Profiling of WDR36 missense variants in German patients with glaucoma. Invest Ophthalmol Vis Sci. 2008 Jan;49(1):270-4. PubMed PMID: 18172102.

A survey of WDR36 mutations to look for association with glaucome. This variant was seen in 4 out of 399 patients and 11 out of 376 controls. This is evidence against any pathogenic effect and, if anything, weak evidence supporting a slightly protective effect.

Footz TK, Johnson JL, Dubois S, Boivin N, Raymond V, Walter MA. Glaucoma-associated WDR36 variants encode functional defects in a yeast model system. Hum Mol Genet. 2009 Apr 1;18(7):1276-87. Epub 2009 Jan 15. PubMed PMID: 19150991.

Functional testing of equivalent substitution in yeast shows no growth defects (table 1). The authors interpret this variant as non-pathogenic based on its presence in controls.

Genomes
 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het CC @ chr5:110436345

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het CC @ chr5:110436345

 

huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het CC @ chr5:110436345

 

Other external references
 

    PolyPhen-2
  • Score: 0.999 (probably damaging)

Other in silico analyses
 

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

Edit history
 

Gene search

"GENE" or "GENE A123C":

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