Implementing ExomeDepth with a variant filter as a CNV-calling tool for germline clinical diagnostic testing

Sammanfattning: Copy number variations (CNVs) cover approximately 4.9 - 9.5% of the human genome. CNVs are involved in both the development of disease and evolutionary adaptions. CNVs play an important part in the development and progression of multiple cardiovascular diseases. CNV calling is traditionally performed with cromosomal microarray (CMA). The advantage of next generation sequensing (NGS) instead of CMA include higher resolution, lower cost and higher sensitivity in detecting smaller CNVs. CNV calling with NGS is connected to a high number of false positives. In this study three different CNV-calling tools for clinical exome sequencing data were evaluated; CoNIFER, CONTRA and ExomeDepth. To further decrease the false positive rate and decrease the hands-on analysis time a variant filter for ExomeDepth was developed and evaluated. However, CNV-calling with clinical exome data is still challenging due to low coverage.