University of Groningen Integration techniques for modern bioinformatics workflows

Today there is a plethora of Locus-Specific Mutation Databases (LSMD) that contain genetic variants for many organisms and for a large range of phenotypes and diseases. This knowledge base is expanding almost daily with the discovery of novel variants in a daily base that have various consequences in human physiology. One of the most widely used standards for reporting new variants is HGVS (Human Genome Variation Society). HGVS describes a variant according to a reference sequence, its position and its nucleotide or amino acid change However, the lack of established quality standards for reporting genetic variants and the plethora of existing reference sequence systems have led to incidental erroneous or ambiguous reporting of variants in LSMDs or even in published reports. Another source of ambiguity is the use of gene names instead of reference sequences in HGVS variants. These inconsistencies hinder the task of identifying the chromosomal position of a HGVS variant, which is a vital part in confirming its existence in a fully genotyped or sequenced sample. Here we review and evaluate the ability of existing tools to infer the genomic position of variants described in HGVS. We also introduce a new tool, MutationInfo, which combines nine existing tools with a BLAT search in order to exhaustively search for the chromosomal position of HGVS variants. To evaluate MutationInfo we applied it to 1,014 variants from dbSNP, 634 HGVS variants that use sequence accession numbers, and 33,337 HGVS variants that use gene names as reference sequences. Its application to dbSNP variants revealed six problematic variants. For HGVS variants with sequence accession numbers it revealed that 129 (20%) could not be analyzed by any individual tool except for MutationInfo’s pipeline. Finally, its application to HGVS variants with gene names revealed the effect of this erratic practice, since half of them could not be unequivocally assigned to a single chromosomal position. Link: http://www.epga.gr/MutationInfo/ Source code: https://github.com/kantale/MutationInfo License: MIT License