title: A curated gene list for reporting results of newborn genomic sequencing.
abstract: Genomic sequencing (GS) for newborns may enable detection of conditions for which early knowledge can improve health outcomes. One of the major challenges hindering its broader application is the time it takes to assess the clinical relevance of detected variants and the genes they impact so that disease risk is reported appropriately.
  
  
  
  To facilitate rapid interpretation of GS results in newborns, we curated a catalog of genes with putative pediatric relevance for their validity based on the ClinGen clinical validity classification framework criteria, age of onset, penetrance, and mode of inheritance through systematic evaluation of published evidence. Based on these attributes, we classified genes to guide the return of results in the BabySeq Project, a randomized, controlled trial exploring the use of newborn GS (nGS), and used our curated list for the first 15 newborns sequenced in this project.
  
  
  
  Here, we present our curated list for 1,514 gene-disease associations. Overall, 954 genes met our criteria for return in nGS. This reference list eliminated manual assessment for 41% of rare variants identified in 15 newborns.
  
  
  
  Our list provides a resource that can assist in guiding the interpretive scope of clinical GS for newborns and potentially other populations.Genet Med advance online publication 12 January 2017.
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ozge
authors.identifier: 0000-0002-4351-6686
authors.initials: O
authors.lastname: Ceyhan-Birsoy
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kalotina
authors.initials: K
authors.lastname: Machini
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Matthew S
authors.identifier: 0000-0002-9733-5207
authors.initials: MS
authors.lastname: Lebo
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Tim W
authors.identifier: 0000-0003-2988-7701
authors.initials: TW
authors.lastname: Yu
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.|Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Pankaj B
authors.identifier: 0000-0003-3255-0456
authors.initials: PB
authors.lastname: Agrawal
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Richard B
authors.identifier: 0000-0002-4326-0609
authors.initials: RB
authors.lastname: Parad
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Ingrid A
authors.identifier: 0000-0003-4712-8821
authors.initials: IA
authors.lastname: Holm
authors.affiliation: Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: McGuire
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Robert C
authors.identifier: 0000-0001-8472-0424
authors.initials: RC
authors.lastname: Green
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.|Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Alan H
authors.identifier: 0000-0001-8818-0568
authors.initials: AH
authors.lastname: Beggs
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rehm
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping / Q000592:standards; D030541:Databases, Genetic; D059472:Exome; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods / Q000592:standards*; D006801:Humans; D007231:Infant, Newborn; D008297:Male