VaRHC: an R package for semi-automation of variant classification in hereditary cancer genes according to ACMG/AMP and gene-specific ClinGen guidelines

Motivation: Germline variant classification allows accurate genetic diagnosis and risk assessment. However, it is a tedious iterative process integrating information from several sources and types of evidence. It should follow gene-specific (if available) or general updated international guidelines....

Descripción completa

Detalles Bibliográficos
Autores: Munté, Elisabet, Feliubadaló, Lidia, Pineda, Marta, Tornero, Eva, Gonzalez, Maribel, Moreno Cabrera, José Marcos, Roca, Carla, Bales Rubio, Joan, Arnaldo, Laura, Capellá, Gabriel, Luis Mosquera, Jose, Lázaro, Conxi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/224336
Acceso en línea:https://hdl.handle.net/2445/224336
Access Level:acceso abierto
Palabra clave:Patologia molecular
Genètica mèdica
Proteïnes supressores de tumors
Molecular pathology
Medical genetics
Tumor suppressor protein
Descripción
Sumario:Motivation: Germline variant classification allows accurate genetic diagnosis and risk assessment. However, it is a tedious iterative process integrating information from several sources and types of evidence. It should follow gene-specific (if available) or general updated international guidelines. Thus, it is the main burden of the incorporation of next-generation sequencing into the clinical setting.Results: We created the vaRiants in HC (vaRHC) R package to assist the process of variant classification in hereditary cancer by: (i) collecting information from diverse databases; (ii) assigning or denying different types of evidence according to updated American College of Molecular Genetics and Genomics/Association of Molecular Pathologist gene-specific criteria for ATM, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, PTEN, and TP53 and general criteria for other genes; (iii) providing an automated classification of variants using a Bayesian metastructure and considering CanVIG-UK recommendations; and (iv) optionally printing the output to an .xlsx file. A validation using 659 classified variants demonstrated the robustness of vaRHC, presenting a better criteria assignment than Cancer SIGVAR, an available similar tool.Availability and implementation: The source code can be consulted in the GitHub repository () Additionally, it will be submitted to CRAN soon.