How is zygosity assigned for mitochondrial variant calls with DRAGEN?

DRAGEN processes chrM (mitochondrial chromosome) through a continuous Allele Frequency (AF) pipeline (similar to the Somatic Variant Calling pipeline). In this case a single ALT allele is considered and the AF is estimated, which can be between 0% and 100%.

A QUAL value is not output in the chrM variant records. Instead, the confidence score is FORMAT/SQ, which gives the Phred-scaled confidence that a variant is present at a given locus. The decision to emit a variant or not is decided by comparing the FORMAT/SQ score to a threshold.

• If FORMAT/SQ < vc-sq-call-threshold, the variant is not output in the variant call file (VCF), and is banded in a <NON_REF> region with FORMAT/GT set to 0/0 (homoplasmic).

• If FORMAT/SQ > vc-sq-call-threshold, the variant is output in the VCF.

  • In DRAGEN v3.x (prior to v4.0.3), the FORMAT/GT is hard coded to 0/1 irrespective of the AF (heteroplasmic).

  • In DRAGEN v4.0.3, the FORMAT/GT is set to 1/1 if FORMAT/AF is > 95% (homoplasmic) and is set to 0/1 if FORMAT/AF is < 95% (heteroplasmic).

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