An enhanced workflow for variant interpretation in UniProtKB/Swiss-Prot improves consistency and reuse in ClinVar.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_7760CD669F21
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
An enhanced workflow for variant interpretation in UniProtKB/Swiss-Prot improves consistency and reuse in ClinVar.
Périodique
Database
Auteur(s)
Famiglietti M.L., Estreicher A., Breuza L., Poux S., Redaschi N., Xenarios I., Bridge A.
Collaborateur(s)
UniProt Consortium
ISSN
1758-0463 (Electronic)
ISSN-L
1758-0463
Statut éditorial
Publié
Date de publication
01/01/2019
Peer-reviewed
Oui
Volume
2019
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Résumé
Personalized genomic medicine depends on integrated analyses that combine genetic and phenotypic data from individual patients with reference knowledge of the functional and clinical significance of sequence variants. Sources of this reference knowledge include the ClinVar repository of human genetic variants, a community resource that accepts submissions from external groups, and UniProtKB/Swiss-Prot, an expert-curated resource of protein sequences and functional annotation. UniProtKB/Swiss-Prot provides knowledge on the functional impact and clinical significance of over 30 000 human protein-coding sequence variants, curated from peer-reviewed literature reports. Here we present a pilot study that lays the groundwork for the integration of curated knowledge of protein sequence variation from UniProtKB/Swiss-Prot with ClinVar. We show that existing interpretations of variant pathogenicity in UniProtKB/Swiss-Prot and ClinVar are highly concordant, with 88% of variants that are common to the two resources having interpretations of clinical significance that agree. Re-curation of a subset of UniProtKB/Swiss-Prot variants according to American College of Medical Genetics and Genomics (ACMG) guidelines using ClinGen tools further increases this level of agreement, mainly due to the reclassification of supposedly pathogenic variants as benign, based on newly available population frequency data. We have now incorporated ACMG guidelines and ClinGen tools into the UniProt Knowledgebase (UniProtKB) curation workflow and routinely submit variant data from UniProtKB/Swiss-Prot to ClinVar. These efforts will increase the usability and utilization of UniProtKB variant data and will facilitate the continuing (re-)evaluation of clinical variant interpretations as data sets and knowledge evolve.
Mots-clé
Copper-transporting ATPases/genetics, Databases, Protein, Genetic Variation, Knowledge Bases, Nerve Tissue Proteins/genetics, Workflow, Zinc Finger Protein Gli3/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/04/2019 8:36
Dernière modification de la notice
16/09/2019 5:26
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