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Recognising the increasing clinical relevance of non-coding variations, there has been an accelerated development of bioinformatics tools dedicated to interpreting non-coding variations, including single-nucleotide variants and copy number variations. Regrettably, most tools remain as either locally installed databases or command-line tools dispersed across diverse online platforms. Such a landscape poses inconveniences and challenges for genetic counsellors seeking to utilise these resources without advanced bioinformatics expertise. Consequently, we developed VarCards2, which incorporates nearly nine billion artificially generated single-nucleotide variants (including those from mitochondrial DNA) and compiles vital annotation information for genetic counselling based on ACMG-AMP variant-interpretation guidelines. These annotations include (I) functional effects; (II) minor allele frequencies; (III) comprehensive function and pathogenicity predictions covering all potential variants, such as non-synonymous substitutions, non-canonical splicing variants, and non-coding variations\u00a0and (IV) gene-level information. Furthermore, VarCards2 incorporates 368\u00a0820\u00a0266 documented short insertions and deletions and 2\u00a0773\u00a0555 documented copy number variations, complemented by their corresponding annotation and prediction tools. In conclusion, VarCards2, by integrating over 150 variant- and gene-level annotation sources, significantly enhances the efficiency of genetic counselling and can be freely accessed at http:\/\/www.genemed.tech\/varcards2\/.<\/jats:p>","DOI":"10.1093\/nar\/gkad1061","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T01:00:05Z","timestamp":1698195605000},"page":"D1478-D1489","source":"Crossref","is-referenced-by-count":27,"title":["VarCards2: an integrated genetic and clinical database for ACMG-AMP variant-interpretation guidelines in the human whole genome"],"prefix":"10.1093","volume":"52","author":[{"given":"Zheng","family":"Wang","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University , Changsha , Hunan\u00a0 410008 , China"},{"name":"Department of Neurology, Xiangya Hospital, Central South University , Changsha , Hunan\u00a0 410008 , China"},{"name":"Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University , Changsha , Hunan 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4033-1843","authenticated-orcid":false,"given":"Guihu","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University , Changsha , Hunan\u00a0 410008 , China"},{"name":"Department of Neurology, Xiangya Hospital, Central South University , Changsha , Hunan\u00a0 410008 , China"},{"name":"Bioinformatics Center, Furong Laboratory & Xiangya Hospital, Central South University , Changsha , Hunan 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaopo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics & Hunan Key Laboratory, School of Life Sciences, Central South University , Changsha , Hunan\u00a0 410008 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University , Changsha , Hunan\u00a0 410008 , China"},{"name":"Bioinformatics Center, Furong Laboratory & Xiangya Hospital, Central South University , Changsha , Hunan 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Xiang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University , Changsha , Hunan\u00a0 410008 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiangya School of Medicine, Central South University , Changsha , Hunan 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Luo","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics & Hunan Key Laboratory, School of Life Sciences, Central South University , Changsha , Hunan\u00a0 410008 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University , Changsha , Hunan\u00a0 410008 , China"},{"name":"Bioinformatics Center, Furong Laboratory & Xiangya Hospital, Central South University , Changsha , Hunan 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Qiu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South 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