Comparison of the ABC and ACMG systems for variant classification.

Autor: Houge G; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway. gunnar.houge@helse-bergen.no., Bratland E; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway., Aukrust I; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway., Tveten K; Department of Medical Genetics, Telemark Hospital Trust, Skien, Norway., Žukauskaitė G; Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania., Sansovic I; Department of Medical and Laboratory Genetics, Endocrinology and Diabetology, Childrens' Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia., Brea-Fernández AJ; Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, CIBERER), Santiago de Compostela, Spain., Mayer K; Center for Human Genetics and Laboratory Diagnostics, MVZ Martinsried GmbH, Martinsried, Germany., Paakkola T; Nordlab Wellbeing Service Group, Genetics Laboratory, Oulu, Finland., McKenna C; Northern Ireland Regional Molecular Diagnostic Service, Belfast, Northern Ireland., Wright W; Northern Ireland Regional Molecular Diagnostic Service, Belfast, Northern Ireland., Markovic MK; Center for Applied and Forensic Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia., Lildballe DL; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Konecny M; Laboratory of Genomic Medicine, GHC GENETICS SK, Bratislava, Slovakia.; Department of Biology, Institute of Biology and Biotechnology, Faculty of Natural Sciences, University of ss. Cyril and Methodius in Trnava, Trnava, Slovakia., Smol T; Institut de Genetique Medicale-CHU Lille, Lille, France., Alhopuro P; HUS Diagnostic Center, Laboratory of Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Gouttenoire EA; MEDISYN Genetics, Chemin d'Entre-Bois 21, Lausanne, Switzerland., Obeid K; Molecular Diagnostics, Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany., Todorova A; Genetic Medico-Diagnostic Laboratory 'Genica' and Genome Center Bulgaria, Sofia, Bulgaria., Jankovic M; Neurology Clinic UCCS, Faculty of Medicine, University of Belgrade, Belgrade, Serbia., Lubieniecka JM; Humangenetik, Ruhr-Universität Bochum, Bochum, Germany., Stojiljkovic M; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia., Buisine MP; Molecular Oncogenetics, Department of Biochemistry and Molecular Biology, Lille University Hospital, Lille, France.; Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277, CANTHER, Lille, France., Haukanes BI; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway., Lorans M; Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark., Roomere H; Department of laboratory genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia., Petit FM; Department of Oncopharmacology, Centre Antoine Lacassagne, Nice, France., Haanpää MK; Department of Genomics, Turku University Hospital, Turku, Finland., Beneteau C; CHU Bordeaux, Service de Génétique Médicale, F-33000, Bordeaux, France., Pérez B; Genetics Department of CEDEM, Universidad Autónoma de Madrid, Madrid, Spain., Plaseska-Karanfilska D; Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', Macedonian Academy of Sciences and Arts, Skopje, North Macedonia., Rath M; Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany.; Department of Human Genetics, University Medicine Greifswald and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany., Fuhrmann N; Institute of Human Genetics, University of Cologne, Cologne, Germany., Ferreira BI; GENELAB by ABC, Faro, Portugal.; Faculty of Medicine and Biomedical Sciences, University of Algarve, Campus de Gambelas, Faro, Portugal., Stephanou C; Molecular Genetics Thalassemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Sjursen W; Department of Medical Genetics, St Olavs Hospital, Trondheim, Norway., Maver A; Clinical Institute of Genomic Medicine, Ljubljana, Slovenia., Rouzier C; Department of Medical Genetics, National Centre for Mitocondrial Diseases, CHU de NICE, Université Côte d'Azur, Nice, France.; CNRS, INSERM, IRCAN, Université Côte d'Azur, Nice, France., Chirita-Emandi A; Department of Microscopic Morphology Genetics Discipline, Center of Genomic Medicine, 'Victor Babes' University of Medicine and Pharmacy Timisoara, Timisoara, Romania., Gonçalves J; Human Genetics Department, National Institute of Health Dr Ricardo Jorge, Lisbon, Portugal., Kuek WCD; Molecular Diagnosis Centre, Department of Laboratory Medicine, National University Hospital, Kent Ridge, Singapore., Broly M; Laboratory of Rare and Autoinflammatory Genetic Diseases, Department of Genetics-LBM, Montpellier University Hospital, Montpellier, France., Haer-Wigman L; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Thong MK; Genetics and Metabolism Unit, Department of Pediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Tae SK; Genetics and Metabolism Unit, Department of Pediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Hyblova M; Department of Genetics, Medirex, Bratislava, Slovakia., den Dunnen JT; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., Laner A; Medizinisch Genetisches Zentrum (MGZ) München, Munich, Germany.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2024 Jul; Vol. 32 (7), pp. 858-863. Date of Electronic Publication: 2024 May 22.
DOI: 10.1038/s41431-024-01617-8
Abstrakt: The ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as "maybe report" after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known.
(© 2024. The Author(s).)
Databáze: MEDLINE
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