Genome Alert!: A standardized procedure for genomic variant reinterpretation and automated gene-phenotype reassessment in clinical routine.

Autor:	Yauy K; Institute for Advanced Biosciences, Centre de recherche UGA / Inserm U 1209 / CNRS UMR 5309, Grenoble, France; SeqOne Genomics, Montpellier, France. Electronic address: kevin.yauy@univ-grenoble-alpes.fr., Lecoquierre F; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, F 76000, Rouen, France., Baert-Desurmont S; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, F 76000, Rouen, France., Trost D; Laboratoire Cerba, Saint-Ouen-l'Aumône, France., Boughalem A; Laboratoire Cerba, Saint-Ouen-l'Aumône, France., Luscan A; Laboratoire Cerba, Saint-Ouen-l'Aumône, France., Costa JM; Laboratoire Cerba, Saint-Ouen-l'Aumône, France., Geromel V; Laboratoire Eurofins Biomnis, Lyon, France., Raymond L; Laboratoire Eurofins Biomnis, Lyon, France., Richard P; Unité Fonctionnelle de Cardiogénétique et Myogénétique, Centre de Génétique, Hôpitaux Universitaire Pitié Salpêtrière-Charles Foix, Paris, France., Coutant S; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, F 76000, Rouen, France., Broutin M; SeqOne Genomics, Montpellier, France., Lanos R; SeqOne Genomics, Montpellier, France., Fort Q; SeqOne Genomics, Montpellier, France., Cackowski S; Grenoble Institut Neurosciences, GIN, Inserm U1216, Université de Grenoble Alpes, Grenoble, France., Testard Q; Institute for Advanced Biosciences, Centre de recherche UGA / Inserm U 1209 / CNRS UMR 5309, Grenoble, France; Laboratoire Eurofins Biomnis, Lyon, France., Diallo A; SeqOne Genomics, Montpellier, France., Soirat N; SeqOne Genomics, Montpellier, France., Holder JM; SeqOne Genomics, Montpellier, France., Duforet-Frebourg N; SeqOne Genomics, Montpellier, France., Bouge AL; SeqOne Genomics, Montpellier, France., Beaumeunier S; SeqOne Genomics, Montpellier, France., Bertrand D; SeqOne Genomics, Montpellier, France., Audoux J; SeqOne Genomics, Montpellier, France., Genevieve D; Medical Genetic Department for Rare Diseases and Personalized Medicine, Montpellier University Hospital, Montpellier, France., Mesnard L; Soins Intensifs Néphrologiques et Rein Aigu, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Paris, France; UMR_S1155, INSERM, Sorbonne Université, Paris, France., Nicolas G; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, F 76000, Rouen, France., Thevenon J; Institute for Advanced Biosciences, Centre de recherche UGA / Inserm U 1209 / CNRS UMR 5309, Grenoble, France., Philippe N; SeqOne Genomics, Montpellier, France.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2022 Jun; Vol. 24 (6), pp. 1316-1327. Date of Electronic Publication: 2022 Mar 17.
DOI:	10.1016/j.gim.2022.02.008
Abstrakt:	Purpose: Retrospective interpretation of sequenced data in light of the current literature is a major concern of the field. Such reinterpretation is manual and both human resources and variable operating procedures are the main bottlenecks. Methods: Genome Alert! method automatically reports changes with potential clinical significance in variant classification between releases of the ClinVar database. Using ClinVar submissions across time, this method assigns validity category to gene-disease associations. Results: Between July 2017 and December 2019, the retrospective analysis of ClinVar submissions revealed a monthly median of 1247 changes in variant classification with potential clinical significance and 23 new gene-disease associations. Re-examination of 4929 targeted sequencing files highlighted 45 changes in variant classification, and of these classifications, 89% were expert validated, leading to 4 additional diagnoses. Genome Alert! gene-disease association catalog provided 75 high-confidence associations not available in the OMIM morbid list; of which, 20% became available in OMIM morbid list For more than 356 negative exome sequencing data that were reannotated for variants in these 75 genes, this elective approach led to a new diagnosis. Conclusion: Genome Alert! (https://genomealert.univ-grenoble-alpes.fr/) enables systematic and reproducible reinterpretation of acquired sequencing data in a clinical routine with limited human resource effect. Competing Interests: Conflict of Interest K.Y., M.B., R.L., Q.F., A.D., N.S., D.B., A.-L.B., and N.D.-F. are partially or fully employed by SeqOne Genomics; J.M-H., S.B, J.A., and N.P. hold shares in SeqOne Genomics; D.T., A.B., A.L., and J.-M.C. are partially or fully employed by Laboratoire Cerba. V.G. and L.R. are partially or fully employed by Laboratoire Eurofins Biomnis. All other authors declare no conflicts of interest. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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