ClinVar: public archive of relationships among sequence variation and human phenotype

Abstract

ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations.

Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations

“…Literature search by PUBMED, ClinVar (Landrum et al. 2014), and Google Scholar were performed to check if the variants had been reported previously.…”

Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk

“…nih.gov/clinvar, accessed on 10 January 2015). 14 The two data files-clinvar.vcf and variant_summary.txt-contain partially overlapping sets of variant records with clinical assertions of pathogenicity. All variants in CFTR that are reported as "pathogenic" or "likely pathogenic" in at least one ClinVar record (as of the date of accession) are included in a "Clinically Annotated As Pathogenic" (CAAP) variant list.…”

“…Within this subset, we identified 131 variants that have been designated "pathogenic" or "likely pathogenic" in at least one report accepted by the curators of the ClinVar database (Supplementary Tables S1 and S2 online). 14 ClinVar-curated variants are separated further into two groups based on annotations and ExAC allele and genotype frequencies as described below. Finally, we identified a third group of 210 variants that have not been clinically annotated but are likely to be disease-contributing based on the properties of the Most platforms are able to capture the majority of pathogenic variants on our combined list for the European populations, but they perform poorly in other populations, especially East Asia.…”

How Far Do We Go With Genetic Evaluation? Gene, Panel, and Tumor Testing

“…Others involved in reclassifying variants include ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) Consortium 35 and ClinVar, a peer-reviewed database funded by the National Institutes of Health, which is a freely available archive of reports of relationships among medically important variants and phenotypes. 36 Professional societies such as the American Medical Association also have adopted positions in favor of data sharing. 37 …”