Curating genomic disease-gene relationships with Gene2Phenotype

Genetically determined disorders are highly heterogenous in clinical presentation and underlying molecular mechanism. The evidence underpinning these conditions in the peer-reviewed literature is variable and requires robust critical evaluation for diagnostic use. Here, we present a structured curation process for the Gene2Phenotype (G2P) project. This draws on multiple lines of clinical, bioinformatic and functional evidence. The process utilises and extends existing terminologies, allows for precise definition of the molecular basis of disease, and confidence levels to be attributed to a given gene-disease assertion. In-depth disease curation using this process will prove useful in applications including in diagnostics, research and the development of targeted therapeutics. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded in whole or in part by the Wellcome Trust [226083/Z/22/Z] for PARADIGM (Primary Annotated Resources to Aid Diagnosis In Genomic Medicine). SEH also received funding from the European Molecular Biology Laboratory. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The G2P data curation template is available as a supplementary file and on the G2P FTP site (http://ftp.ebi.ac.uk/pub/databases/gene2phenotype/).The datasets generated through the process described in the current study are available in the G2P repository, www.ebi.ac.uk/gene2phenotype/downloads.