title: Evaluation of autosomal dominant retinal dystrophy genes in an unaffected cohort suggests rare or private missense variants may often be benign.
abstract: BACKGROUND
  Many genes have been reported as harboring autosomal dominant mutations causing retinal dystrophy. As newly available gene panel sequencing and whole exome sequencing will open these genes up to greater scrutiny, we assess the rate of rare coding variation in these genes among unaffected individuals to provide context for variants that will be discovered when clinical subjects are sequenced.
  
  
  METHODS
  Publicly available data from the Exome Variant Project were analyzed, focusing on 36 genes known to harbor mutations causing autosomal dominant macular dystrophy.
  
  
  RESULTS
  Rates of rare (minor allele frequency ≤0.1%) and private missense variants within autosomal dominant retinal dystrophy genes were found to occur at a high frequency in unaffected individuals, while nonsense variants were not.
  
  
  CONCLUSIONS
  We conclude that rare missense variations in most of these genes identified in individuals with retinal dystrophy cannot be confidently classified as disease-causing in the absence of additional information such as linkage or functional validation.
authors.affiliation: Jules Stein Eye Institute, University of California, Los Angeles, CA 90095, USA.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Strom
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gorin
mesh_terms: D018389:Codon, Nonsense / Q000235:genetics; D015331:Cohort Studies; D030541:Databases, Genetic; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D058499:Retinal Dystrophies / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense