Jessica Ezzell Hunter1, Charisma L Jenkins2, Joanna E Bulkley2, Marian J Gilmore2, Kristy Lee3, Christine M Pak2, Kathleen E Wallace3, Adam H Buchanan4, Ann Katherine M Foreman3, Amanda S Freed5, Scott Goehringer4, Kandamurugu Manickam6, Naomi J L Meeks7, Erin M Ramos8, Neethu Shah9, Robert D Steiner10, Sai Lakshmi Subramanian9, Tracy Trotter11, Elizabeth M Webber12, Marc S Williams4, Katrina A B Goddard2, Bradford C Powell3. 1. Genomics, Ethics, and Translational Research Program, RTI International, ResearchTriangle Park, NC. Electronic address: jehunter@rti.org. 2. Department of Translational and Applied Genomics (TAG), Kaiser Permanente Center for Health Research, Portland, OR. 3. Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. 4. Genomic Medicine Institute, Geisinger, Danville, PA. 5. Department of Clinical Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA. 6. Division of Genetic and Genomic Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; The Ohio State University College of Medicine, Columbus, OH. 7. Section of Genetics and Metabolism, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO. 8. Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. 9. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX. 10. School of Medicine and Public Health, University of Wisconsin, Madison, WI. 11. John Muir Health, Walnut Creek, CA. 12. Kaiser Permanente Center for Health Research, Portland, OR.
Abstract
PURPOSE: Synthesis and curation of evidence regarding the clinical actionability of secondary findings (SFs) from genome-scale sequencing are needed to support decision-making on reporting of these findings. To assess actionability of SFs in children and adolescents, the Clinical Genome Resource established the Pediatric Actionability Working Group (AWG). METHODS: The Pediatric AWG modified the framework of the existing Adult AWG, which included production of summary reports of actionability for genes and associated conditions and consensus actionability scores for specific outcome-intervention pairs. Modification of the adult framework for the pediatric setting included accounting for special considerations for reporting presymptomatic or predictive genetic findings in the pediatric context, such as maintaining future autonomy by not disclosing conditions not actionable until adulthood. The Pediatric AWG then applied this new framework to genes and associated conditions with putative actionability. RESULTS: As of September 2021, the Pediatric AWG applied the new framework to 70 actionability topics representing 143 genes. Reports and scores are publicly available at www.clinicalgenome.org. CONCLUSION: The Pediatric AWG continues to curate gene-condition topics and build an evidence-based resource, supporting clinical communities and decision-makers with policy development on the return of SFs in pediatric populations.
PURPOSE: Synthesis and curation of evidence regarding the clinical actionability of secondary findings (SFs) from genome-scale sequencing are needed to support decision-making on reporting of these findings. To assess actionability of SFs in children and adolescents, the Clinical Genome Resource established the Pediatric Actionability Working Group (AWG). METHODS: The Pediatric AWG modified the framework of the existing Adult AWG, which included production of summary reports of actionability for genes and associated conditions and consensus actionability scores for specific outcome-intervention pairs. Modification of the adult framework for the pediatric setting included accounting for special considerations for reporting presymptomatic or predictive genetic findings in the pediatric context, such as maintaining future autonomy by not disclosing conditions not actionable until adulthood. The Pediatric AWG then applied this new framework to genes and associated conditions with putative actionability. RESULTS: As of September 2021, the Pediatric AWG applied the new framework to 70 actionability topics representing 143 genes. Reports and scores are publicly available at www.clinicalgenome.org. CONCLUSION: The Pediatric AWG continues to curate gene-condition topics and build an evidence-based resource, supporting clinical communities and decision-makers with policy development on the return of SFs in pediatric populations.
Authors: Elizabeth M Webber; Jessica Ezzell Hunter; Leslie G Biesecker; Adam H Buchanan; Elizabeth V Clarke; Erin Currey; Orit Dagan-Rosenfeld; Kristy Lee; Noralane M Lindor; Christa Lese Martin; Aleksandar Milosavljevic; Kathleen F Mittendorf; Kristin R Muessig; Julianne M O'Daniel; Ronak Y Patel; Erin M Ramos; Shannon Rego; Anne M Slavotinek; Nara Lygia M Sobriera; Meredith A Weaver; Marc S Williams; James P Evans; Katrina A B Goddard Journal: Hum Mutat Date: 2018-11 Impact factor: 4.878
Authors: Sarah S Kalia; Kathy Adelman; Sherri J Bale; Wendy K Chung; Christine Eng; James P Evans; Gail E Herman; Sophia B Hufnagel; Teri E Klein; Bruce R Korf; Kent D McKelvey; Kelly E Ormond; C Sue Richards; Christopher N Vlangos; Michael Watson; Christa L Martin; David T Miller Journal: Genet Med Date: 2016-11-17 Impact factor: 8.822
Authors: David T Miller; Kristy Lee; Wendy K Chung; Adam S Gordon; Gail E Herman; Teri E Klein; Douglas R Stewart; Laura M Amendola; Kathy Adelman; Sherri J Bale; Michael H Gollob; Steven M Harrison; Ray E Hershberger; Kent McKelvey; C Sue Richards; Christopher N Vlangos; Michael S Watson; Christa Lese Martin Journal: Genet Med Date: 2021-05-20 Impact factor: 8.822
Authors: Robert C Green; Jonathan S Berg; Wayne W Grody; Sarah S Kalia; Bruce R Korf; Christa L Martin; Amy L McGuire; Robert L Nussbaum; Julianne M O'Daniel; Kelly E Ormond; Heidi L Rehm; Michael S Watson; Marc S Williams; Leslie G Biesecker Journal: Genet Med Date: 2013-06-20 Impact factor: 8.822
Authors: Lainie Friedman Ross; Laine Friedman Ross; Howard M Saal; Karen L David; Rebecca R Anderson Journal: Genet Med Date: 2013-02-21 Impact factor: 8.822
Authors: Jessica Ezzell Hunter; Stephanie A Irving; Leslie G Biesecker; Adam Buchanan; Brian Jensen; Kristy Lee; Christa Lese Martin; Laura Milko; Kristin Muessig; Annie D Niehaus; Julianne O'Daniel; Margaret A Piper; Erin M Ramos; Sheri D Schully; Alan F Scott; Anne Slavotinek; Nara Sobreira; Natasha Strande; Meredith Weaver; Elizabeth M Webber; Marc S Williams; Jonathan S Berg; James P Evans; Katrina A B Goddard Journal: Genet Med Date: 2016-04-28 Impact factor: 8.822