GeVaCT - Genomic Variant Classifier Tool

High throughput screening (HTS) techniques, like mendeliome, whole exome and genome screening, are becoming a routine in a clinical diagnostic setting. However, classifying the identified genomic variants as benign or(likely) pathogenic, is still a tedious and time consuming process for the(clinical) geneticist. To facilitate this variant classification process, we have developed GeVaCT, a standalone Java based tool that implements and automatizes a published variant classification scheme for autosomal dominant disorders. GeVaCT currently supports annotated variant files from Alamut Batch (Interactive Biosoftware), with future plans to support input from other variant annotation tools.
The variant classification process currently implemented in GeVaCT is based on a published scheme in the context of cardiac arrhythmias (Hofman et al.,2013). The implemented scheme consists of two phases: pre-processing and variant classification. During pre-processing, the annotated variant file from Alamut Batch is imported and filtered based on the presence of the variant in databases with described variants or a local database, the variant location,the coding effect and the variant allele frequency in an ethnically matched population. The variant classification workflow depends on the type of variant: either missense or nonsense/frame-shift. Each attribute used gets a weighted score that is summed up with the others to come to a first variant classification. This first score is updated based on familial and functional information obtained for the variant-of-interest. The final result is a classification of the variant in one out of five classes ranging from non-pathogenic to pathogenic.