LRRK2 A419V - GET-Evidence

Curation:
Currentness:

LRRK2 A419V

(LRRK2 Ala419Val)


Short summary

Reported to cause autosomal dominant Parkinson’s disease. This report is recorded in ClinVar, submitted by GeneReviews (http://www.ncbi.nlm.nih.gov/clinvar/RCV000032405/). However, one publication linked by ClinVar, Di Fonzo 2006 (PMID: 16633828) found the variant with equal frequency in cases and controls in a study of Taiwanese cases and controls. According to ExAC, this variant has a much higher allele frequency in east asians (0.58%) where 1 in 90 carry the variant. This strongly contradicts the variant as causing this disease, and this reported effect should be considered disproven.

Variant evidence
Computational 4

High frequency in East Asian ancestry strongly contradicts hypothesized effect

Functional -
Case/Control 4

Equal frequency in cases and controls

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, benign

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • None available.

Publications
 

Di Fonzo A, Wu-Chou YH, Lu CS, van Doeselaar M, Simons EJ, Rohé CF, Chang HC, Chen RS, Weng YH, Vanacore N, Breedveld GJ, Oostra BA, Bonifati V. A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan. Neurogenetics. 2006 Jul;7(3):133-8. Epub 2006 Apr 22. PubMed PMID: 16633828.

 

Genomes
 

Other external references
 

Other in silico analyses
 

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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