Japanese pathogenic variant database: DPV

Abstract

Abstract. Databases of pathogenic variants form the basis for clinical genomic diagnosis using next-generation sequencers. ClinVar and the Human Gene Mutation Database (HGMD) are two major databases for pathogenic variants. However, ethnic diversity in the distributions of pathogenic variants in these databases has been observed; thus, geographic region-specific variant databases are required. We established a Japanese pathogenic variant database in 2016 and began registering pathogenic variants from published articles written by Japanese researchers. The criteria for registration are as follows: 1) the variant has been validated using Sanger sequencing, 2) the minor allele frequency of the variant is lower than 0.03 in the normal Japanese population, and 3) the clinical features of the patient have been critically evaluated by multiple clinicians and geneticists. All registered variants can be downloaded as an aggregated single VCF file to use in laboratories. We are presently curating variants from more than 2000 articles and estimate the registration of >10,000 pathogenic variants derived from the Japanese population. Although the number of registered variants remains relatively small, the clinical genetics community in Japan has begun to work on this initiative in a concerted manner.

MvPPT: a highly efficient and sensitive pathogenicity prediction tool for missense variants

“…For assessment, we collected variants from VariSNP (46), VKGL (47), DPV (48), DoCM (49), MetaLR/SVM_Test (9), and CAPICE_Test (19), to generate an independent test set. Variants that were used in any training set or in our features’ training data were discarded from test sets, and only variants with comprehensive scores required by all comparators were included.…”

mvPPT: A Highly Efficient and Sensitive Pathogenicity Prediction Tool for Missense Variants

“…An independent test set was generated by combining variants from Vereniging Klinisch Genetische Laboratoriumdiagnostiek (VKGL, 2020.9) [36] , VariSNP (2017.2.16) [37] , Database of Curated Mutations (DoCM, version 3.2) [38] , Database of Pathogenic Variants (DPV, 2020.12.29) [39] , Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome (CAPICE, version 4) test [19] , and MetaLR/SVM_Test [9] . To guarantee a second independent test set with variants that have never been used in any tools’ training set, we used PubMed to search for papers reporting new genetic disease-causing genes.…”

Medical genetics and genomic medicine in Japan

“…Therefore, public pathological variant databases need to be constructed and utilized. The project program for an Integrated Database of Clinical and Genomic Information by AMED has aimed to develop pathological variant database among Japanese patients (Database of Pathogenic Variants: http://dpv.cmg.med.keio.ac.jp/dpv-pub/top, Medical Genomics Japan Variant Database: https://mgend.med.kyoto-u.ac.jp/) (Suzuki et al, ).…”