Gene-specific ACMG/AMP classification criteria for germline APC variants: Recommendations from the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel.

Autor:	Spier I; Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany; National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany; European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) - Project ID No 739547., Yin X; Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany; Department of Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, Australia; Department of Medicine, University of Melbourne, Parkville, Australia. Electronic address: xiaoyu.yin@mh.org.au., Richardson M; Ambry Genetics, Aliso Viejo, CA., Pineda M; European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) - Project ID No 739547; Hereditary Cancer Program, Catalan Institute of Oncology - ONCOBELL, IDIBELL, Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Salud Carlos III, Madrid, Spain., Laner A; Medical Genetics Center Munich, MGZ Munich, Germany., Ritter D; Baylor College of Medicine, Houston, TX; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX., Boyle J; Department of Oncological Sciences, School of Medicine, University of Utah, Salt Lake City, UT., Mur P; Hereditary Cancer Program, Catalan Institute of Oncology - ONCOBELL, IDIBELL, Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Salud Carlos III, Madrid, Spain., Hansen TVO; Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Shi X; Greenwood Genetic Center, Greenwood, SC., Mahmood K; Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, Parkville, Australia; Melbourne Bioinformatics, University of Melbourne, Parkville, Australia., Plazzer JP; Department of Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, Australia., Ognedal E; Haukeland University Hospital, Bergen, Norway., Nordling M; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Clinical Genetics, Linköping University Hospital, Linköping, Sweden., Farrington SM; Cancer Research UK Edinburgh Centre, the University of Edinburgh, Edinburgh, United Kingdom., Yamamoto G; Department of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan., Baert-Desurmont S; Department of Genetics, Rouen University Hospital, Rouen, France., Martins A; Department of Genetics, Rouen University Hospital, Rouen, France., Borras E; Invitae, San Francisco, CA., Tops C; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., Webb E; GeneDx, Gaithersburg, MD., Beshay V; Peter MacCallum Cancer Centre, Melbourne, Australia., Genuardi M; Fondazione Policlinico Universitario A. Gemelli IRCCS, and Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy., Pesaran T; Ambry Genetics, Aliso Viejo, CA., Capellá G; European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) - Project ID No 739547; Hereditary Cancer Program, Catalan Institute of Oncology - ONCOBELL, IDIBELL, Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Salud Carlos III, Madrid, Spain., Tavtigian SV; Department of Oncological Sciences, School of Medicine, University of Utah, Salt Lake City, UT; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT., Latchford A; Polyposis Registry, St. Mark's Hospital, London, United Kingdom; Department of Surgery and Cancer, Imperial College, London, United Kingdom., Frayling IM; Polyposis Registry, St. Mark's Hospital, London, United Kingdom; Inherited Tumour Syndromes Research Group, Institute of Cancer & Genetics, Cardiff University, United Kingdom., Plon SE; Baylor College of Medicine, Houston, TX; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX., Greenblatt M; Larner College of Medicine, University of Vermont, Burlington, VT., Macrae FA; Department of Colorectal Medicine and Genetics, Royal Melbourne Hospital, Parkville, Australia; Department of Medicine, University of Melbourne, Parkville, Australia., Aretz S; Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany; National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany; European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) - Project ID No 739547.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Feb; Vol. 26 (2), pp. 100992. Date of Electronic Publication: 2023 Oct 04.
DOI:	10.1016/j.gim.2023.100992
Abstrakt:	Purpose: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome. Methods: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants. Results: The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS). Conclusion: The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use. Competing Interests: Conflict of Interest SEP is a member of the scientific advisory panel of Baylor Genetics Laboratories. All other authors declare no conflicts of interest. Ethics Declaration This study was conducted in accordance with the guidelines of the Ethics Committee of the Medical Faculty of the University of Bonn and the 1975 Declaration of Helsinki. Participants of clinical genetic testing gave written informed consent for their data to be used for clinical research and genetic investigations according to local regulations. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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