A variant by any name: quantifying annotation discordance across tools and clinical databases

BioRxiv : the Preprint Server for Biology
Jennifer L YenDeanna M Church


Background: Clinical genomic testing is dependent on the robust identification and reporting of variant-level information in relation to disease. With the shift to high-throughput sequencing, a major challenge for clinical diagnostics is the cross-identification of variants called on their genomic position to resources that rely on transcript- or protein-based descriptions. Methods: We evaluated the accuracy of three tools (SnpEff, Variant Effect Predictor and Variation Reporter) that generate transcript and protein-based variant nomenclature from genomic coordinates according to guidelines by the Human Genome Variation Society (HGVS). Our evaluation was based on comparisons to a manually-curated list of 127 test variants of various types drawn from data sources, each with HGVS-compliant transcript and protein descriptors. We further evaluated the concordance between annotations generated by Snpeff and Variant Effect Predictor with those in major germline and cancer databases: ClinVar and COSMIC, respectively. Results: We find that there is substantial discordance between the annotation tools and databases in the description of insertion and/or deletions. Accuracy based on our ground truth set was between 80-90% for coding and ...Continue Reading

Related Concepts

Malignant Neoplasms
Gene Deletion
Laboratory Procedures
Health Care
Gene Mutant

Related Feeds

Cancer Genomics (Preprints)

Cancer genomics employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest preprints here.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.