CYP2D6 Caller

The CYP2D6 caller is capable of genotyping the CYP2D6 gene from whole-genome sequencing (WGS) data and is derived from the method implemented in Cyrius¹. Due to high sequence similarity with its pseudogene paralog CYP2D7 and a wide variety of common structural variants (SVs), a specialized caller is necessary to resolve variants and identify likely star allele haplotypes.

The CYP2D6 Caller performs the following steps:

1. Determines total CYP2D6 and CYP2D7 copy number from read depth.
2. Determines CYP2D6-derived copy number at CYP2D6/CYP2D7 differentiating sites.
3. Detects SV breakpoints by calculating the changes in CYP2D6-derived copy number along the CYP2D6 gene.
4. Calls small variants in CYP2D6 copies.
5. Identifies star alleles from the detected SV breakpoints and small variants.
6. Identifies the most likely genotype for the called star alleles.

The CYP2D6 Caller requires whole-genome sequencing (WGS) data aligned to a human reference genome with at least 30x coverage.