ClinGen Allele Registry links information about genetic variants
Open Access
- 11 October 2018
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 39 (11), 1690-1701
- https://doi.org/10.1002/humu.23637
Abstract
Effective exchange of information about genetic variants is currently hampered by the lack of readily available globally unique variant identifiers that would enable aggregation of information from different sources. The ClinGen Allele Registry addresses this problem by providing (1) globally unique “canonical” variant identifiers (CAids) on demand, either individually or in large batches; (2) access to variant‐identifying information in a searchable Registry; (3) links to allele‐related records in many commonly used databases; and (4) services for adding links to information about registered variants in external sources. A core element of the Registry is a canonicalization service, implemented using in‐memory sequence alignment‐based index, which groups variant identifiers denoting the same nucleotide variant and assigns unique and dereferenceable CAids. More than 650 million distinct variants are currently registered, including those from gnomAD, ExAC, dbSNP, and ClinVar, including a small number of variants registered by Registry users. The Registry is accessible both via a web interface and programmatically via well‐documented Hypertext Transfer Protocol (HTTP) Representational State Transfer Application Programming Interface (REST‐APIs). For programmatic interoperability, the Registry content is accessible in the JavaScript Object Notation for Linked Data (JSON‐LD) format. We present several use cases and demonstrate how the linked information may provide raw material for reasoning about variant's pathogenicity.Funding Information
- National Human Genome Research Institute (U41HG006834 (Rehm), U41HG009649 (Bustamante), U41HG009650 (Berg), U01HG007436 (Bustamante), U01HG007437 (Berg), HHSN261200800001E)
This publication has 22 references indexed in Scilit:
- Genomic variant annotation and prioritization with ANNOVAR and wANNOVARNature Protocols, 2015
- CSN and CAVA: variant annotation tools for rapid, robust next-generation sequencing analysis in the clinical settingGenome Medicine, 2015
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular PathologyGenetics in Medicine, 2015
- Unified representation of genetic variantsBioinformatics, 2015
- COSMIC: exploring the world's knowledge of somatic mutations in human cancerNucleic Acids Research, 2014
- Locus Reference Genomic: reference sequences for the reporting of clinically relevant sequence variantsNucleic Acids Research, 2013
- wANNOVAR: annotating genetic variants for personal genomes via the webJournal of Medical Genetics, 2012
- LOVD v.2.0: the next generation in gene variant databasesHuman Mutation, 2011
- ANNOVAR: functional annotation of genetic variants from high-throughput sequencing dataNucleic Acids Research, 2010
- dbSNP: the NCBI database of genetic variationNucleic Acids Research, 2001