In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) and insertions/deletions (indels)). Since then, Whole Genome Sequencing (WGS) has been increasingly introduced in the diagnosis of rare diseases as WGS allows the simultaneous detection of SNVs, Structural Variants (SVs) and other types of variants such as repeat expansions. The use of WGS in diagnostics warrants the re-evaluation and update of previously published guidelines. This work was jointly initiated by EuroGentest and the Horizon2020 project Solve-RD. Statements from the 2016 guidelines have been reviewed in the context of WGS and updated where necessary. The aim of these recommendations is primarily to list the points to consider for clinical (laboratory) geneticists, bioinformaticians, and (non-)geneticists, to provide technical advice, aid clinical decision-making and the reporting of the results.

Agilent Technologies Diagnostics and Genomics Group Leuven Belgium

Amsterdam University Medical Centers location AMC Department of Clinical Genetics Amsterdam The Netherlands

Center for Human Genetics KU Leuven Gasthuisberg Laboratory for Molecular Diagnosis Leuven Belgium

Center for Medical Genetics Ghent University Hospital Ghent Belgium

CENTOGENE GmbH Am Strande 7 18055 Rostock Germany

CNAG CRG Centre for Genomic Regulation The Barcelona Institute of Science and Technology Barcelona Spain

Departament de Genètica Microbiologia i Estadística Facultat de Biologia Universitat de Barcelona Barcelona Spain

Department of biology and medical genetics 2nd Faculty of Medicine Charles University and University hospital Motol Prague Czechia

Department of Biomolecular Medicine Ghent University Ghent Belgium

Department of Genetics University Medical Center Groningen University Groningen Groningen The Netherlands

Department of Human Genetics and Donders Centre for Cognitive Neuroscience Radboud University Medical Center Nijmegen The Netherlands

Department of Human Genetics and Radboud Institute for Molecular Life Sciences Radboud University Medical Centre Nijmegen 6525 GA The Netherlands

Department of Medical Genetics Haukeland University Hospital 5021 Bergen Norway

Department of Oncology and Metabolism University of Sheffield Sheffield UK

Dept of Clinical Genetics Box 134 Cambridge University Hospitals Cambridge UK

Dept of Pediatric Surgery Rigshospitalet Faculty of Health and Medical Sciences Copenhagen University Denmark Dept of Women's and Children's health Karolinska Institute Stockholm Sweden

Division of Evolution and Genomic Sciences School of Biological Sciences University of Manchester Manchester UK

Erasmus MC University Medical Center Sophia Children's Hospital Department of Clinical Genetics Rotterdam The Netherlands

Genomics Quality Assessment NHS Lothian Edinburgh Scotland

German Center for Neurodegenerative Diseases Tübingen Germany

Hertie Institute for Clinical Brain Research University of Tübingen Tübingen Germany

Highly Specialised Osteogenesis Imperfecta Service and Sheffield Clinical Genetics Service Sheffield Children's NHS Foundation Trust Sheffield UK

Illumina Inc Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA

Institute of Medical Genetics and Applied Genomics University of Tübingen Tübingen Germany

Jena University Hospital Friedrich Schiller University Institute of Human Genetics Jena Germany

Lehrstuhl für Sozialpädiatrie Technische Universität München Munich Germany

Manchester Centre For Genomic Medicine University of Manchester St Mary's Hospital Manchester M13 9WL UK

MVZ Martinsried GmbH Martinsried Germany

Pediatric Neurology reference centre for rare epilepsies Hôpital Necker Enfants malades APHP Université de Paris Institut Imagine Paris France

Radboud university medical center Department of Human Genetics P O Box 9101 6500 HB Nijmegen The Netherlands

Unit of Medical Genetics University Hospital and Department of Medical Sciences University of Ferrara Ferrara Italy

Universitat Pompeu Fabra Barcelona Spain

University Hospital Tübingen Institute for Medical Genetics and Applied Genomics and Centre for Rare Diseases Calwerstr 7 72076 Tübingen Germany

Zentrum für Humangenetik und Laboratoriumsdiagnostik Martinsried Germany

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Review of the Relationships Between Human Gut Microbiome, Diet, and Obesity

Validated WGS and WES protocols proved saliva-derived gDNA as an equivalent to blood-derived gDNA for clinical and population genomic analyses