title: Incidentalome from Genomic Sequencing: A Barrier to Personalized Medicine?
abstract: BACKGROUND
  In Western cohorts, the prevalence of incidental findings (IFs) or incidentalome, referring to variants in genes that are unrelated to the patient's primary condition, is between 0.86% and 8.8%. However, data on prevalence and type of IFs in Asian population is lacking.
  
  
  METHODS
  In 2 cohorts of individuals with genomic sequencing performed in Singapore (total n = 377), we extracted and annotated variants in the 56 ACMG-recommended genes and filtered these variants based on the level of pathogenicity. We then analyzed the precise distribution of IFs, class of genes, related medical conditions, and potential clinical impact.
  
  
  RESULTS
  We found a total of 41,607 variants in the 56 genes in our cohort of 377 individuals. After filtering for rare and coding variants, we identified 14 potential variants. After reviewing primary literature, only 4 out of the 14 variants were classified to be pathogenic, while an additional two variants were classified as likely pathogenic. Overall, the cumulative prevalence of IFs (pathogenic and likely pathogenic variants) in our cohort was 1.6%.
  
  
  CONCLUSIONS
  The cumulative prevalence of IFs through genomic sequencing is low and the incidentalome may not be a significant barrier to implementation of genomics for personalized medicine.
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Paediatric Academic Clinical Programme, Singhealth Duke-NUS Graduate Medical School, Singapore.
authors.forename: Saumya Shekhar
authors.initials: SS
authors.lastname: Jamuar
authors.affiliation: Genome Institute of Singapore, ASTAR, Singapore; Cardiovascular Research Institute, National University of Singapore, National University Health System, Singapore.
authors.forename: Jyn Ling
authors.initials: JL
authors.lastname: Kuan
authors.affiliation: KK Research Center, KK Women's and Children's Hospital, Singapore.
authors.forename: Maggie
authors.initials: M
authors.lastname: Brett
authors.affiliation: Genome Institute of Singapore, ASTAR, Singapore; Cardiovascular Research Institute, National University of Singapore, National University Health System, Singapore.
authors.forename: Zenia
authors.initials: Z
authors.lastname: Tiang
authors.affiliation: Genome Institute of Singapore, ASTAR, Singapore; Cardiovascular Research Institute, National University of Singapore, National University Health System, Singapore.
authors.forename: Wilson Lek Wen
authors.initials: WL
authors.lastname: Tan
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, Singapore.
authors.forename: Jiin Ying
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Paediatric Academic Clinical Programme, Singhealth Duke-NUS Graduate Medical School, Singapore.
authors.forename: Wendy Kein Meng
authors.initials: WK
authors.lastname: Liew
authors.affiliation: Genome Institute of Singapore, ASTAR, Singapore.
authors.forename: Asif
authors.initials: A
authors.lastname: Javed
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, Singapore.
authors.forename: Woei Kang
authors.initials: WK
authors.lastname: Liew
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Paediatric Academic Clinical Programme, Singhealth Duke-NUS Graduate Medical School, Singapore.
authors.forename: Hai Yang
authors.initials: HY
authors.lastname: Law
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Paediatric Academic Clinical Programme, Singhealth Duke-NUS Graduate Medical School, Singapore.
authors.forename: Ee Shien
authors.initials: ES
authors.lastname: Tan
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Paediatric Academic Clinical Programme, Singhealth Duke-NUS Graduate Medical School, Singapore.
authors.forename: Angeline
authors.initials: A
authors.lastname: Lai
authors.affiliation: Department of Paediatrics, KK Women's and Children's Hospital, Singapore; Paediatric Academic Clinical Programme, Singhealth Duke-NUS Graduate Medical School, Singapore.
authors.forename: Ivy
authors.initials: I
authors.lastname: Ng
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Yik Ying
authors.initials: YY
authors.lastname: Teo
authors.affiliation: Institute of Molecular and Cell Biology, ASTAR, Singapore.
authors.forename: Byrappa
authors.initials: B
authors.lastname: Venkatesh
authors.affiliation: Institute of Medical Biology, ASTAR, Singapore.
authors.forename: Bruno
authors.initials: B
authors.lastname: Reversade
authors.affiliation: KK Research Center, KK Women's and Children's Hospital, Singapore.
authors.forename: Ene Choo
authors.initials: EC
authors.lastname: Tan
authors.affiliation: Genome Institute of Singapore, ASTAR, Singapore; Cardiovascular Research Institute, National University of Singapore, National University Health System, Singapore.
authors.forename: Roger
authors.initials: R
authors.lastname: Foo
mesh_terms: D002874:Chromosome Mapping; D030541:Databases, Genetic; D059472:Exome / Q000235:genetics; D014644:Genetic Variation; D015894:Genome, Human; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D033162:Incidental Findings; D058977:Molecular Sequence Annotation; D009154:Mutation; D057285:Precision Medicine; D012846:Singapore
keywords: Genomic sequencing; Incidental findings; Personalized medicine