Genome Alert!: A standardized procedure for genomic variant reinterpretation and automated gene-phenotype reassessment in clinical routine.
ClinVar
Gene–phenotype associations
Sequencing reinterpretation
Variant pathogenicity
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
30
11
2021
revised:
07
02
2022
accepted:
07
02
2022
pubmed:
22
3
2022
medline:
3
6
2022
entrez:
21
3
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 35311657
pii: S1098-3600(22)00654-2
doi: 10.1016/j.gim.2022.02.008
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1316-1327Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
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.