VWF G2705R - GET-Evidence

Curation:
Currentness:

VWF G2705R

(VWF Gly2705Arg)


Short summary

Probably benign, seems to be considered an uncommon polymorphism.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional -
Case/Control 1

Uncommon, but not rare — allele frequency supports no strong pathogenic effect

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

“Mutation analysis in type 1 von Willebrand disease patients entered in the multicenter MCMDM-1VWD study” (Goodeve et al) http://blackwellpublishing.com/isth2003/abstract.asp?id=7788
This mentions the variant along with other VWF variants found in 95 cases. They don’t mention how many but, given the allele frequency of this variant, it is unsurprising that they report seeing it.

Allele frequency

  • T @ chr12:6061559: 4.6% (495/10758) in EVS
  • T @ chr12:5931819: 3.1% (4/128) in GET-Evidence
  • Frequency shown in summary reports: 4.6% (495/10758)

Publications
 

Surdhar GK, Enayat MS, Lawson S, Williams MD, Hill FG. Homozygous gene conversion in von Willebrand factor gene as a cause of type 3 von Willebrand disease and predisposition to inhibitor development. Blood. 2001 Jul 1;98(1):248-50. PubMed PMID: 11439975.

This variant was seen downstream of a homozygous gene conversion (which caused a nonsense mutation) seen in a case with type 3 von Willebrand disease in a consanguineous family. This implies it is a nonpathogenic polymorphism.

Genomes
 

Other external references
 

    dbSNP
  • rs7962217
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.992 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 6
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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