VANCOUVER, British Columbia (GenomeWeb) – Illumina announced yesterday that it has submitted more than 95,000 human genetic variants to the National Center for Biotechnology Information (NCBI)'s open-access ClinVar database.
The variants were identified in individuals undergoing TruGenome predisposition testing or TruGenome undiagnosed disease testing at the company's CLIA-certified, CAP-accredited Illumina Clinical Services Laboratory, Ryan Taft, senior director of scientific research, told GenomeWeb at the American Society of Human Genetics annual meeting.
Partners Healthcare Personalized Medicine Laboratory for Molecular Medicine Director Heidi Rehm began developing ClinVar with NCBI several years ago in an effort to create a clinically curated repository of variants in the human genome.
Standardized guidelines established by the American College of Medical Genetics and Genomics, the Association for Molecular Pathology, and the College of American Pathologists and published in Genetics in Medicine last year laid out the criteria for designating variants as "pathogenic," "likely pathogenic," "likely benign," "benign," or of "uncertain significance."
The collection of variants donated by Illumina — which includes everything from pathogenic and likely pathogenic variants to benign variants and variants of unknown significance — is the largest contribution to ClinVar from a single source, Rehm told GenomeWeb in an email message.
With the newly submitted collection of variants from individuals assessed at the Illumina Clinical Services Laboratory, it should be possible to begin resolving more and more of the contentious variant classifications in ClinVar, Illumina Vice President and Chief Scientist David Bentley noted. Each donated variant was re-curated based on updated information available in databases such as ExAC, which is aggregating and harmonizing exome sequencing data from a variety of projects.
The Illumina team was agnostic in its identification of variants curated for ClinVar, focusing on single nucleotide changes, small insertions and deletions, and copy number variants that turned up during disease pre-disposition or undiagnosed disease testing.
Taft explained that most of those variants were identified in individuals on the pre-disposition testing side, which involves whole-genome sequencing to around 30-fold average coverage followed by analyses that focused on 1,691 genes that were previously associated with more than 1,200 conditions.
The set donated to ClinVar this week was identified using sequence data for 1,335 genomes sequenced for predisposition testing and 269 genomes sequenced in an effort to find genetic explanations for undiagnosed diseases, Taft said. These variants were submitted to ClinVar along with all of the relevant interpretation and assertion criteria.
Illumina has developed an in-house variant management system for dealing with variants detected during whole-genome sequencing-based testing. Its data is stored on site behind a firewall to maintain patient privacy.
The firm plans to continue donating curated human variant information to ClinVar as it becomes available, both through prospective sequencing and retrospective analyses of existing sequence data.