An allele of a proband variant is de novo if it does not appear in the genotype of either of the proband's parents at this variant position.

The category HasDeNovoNonRefAllele is assigned to a proband variant if the variant meets all of the following criteria:

  • The variant has an allele that:
    • Is not the same as the reference allele
    • Does not appear in the father's genotype
    • Does not appear in the mother's genotype
  • The coverage of the father's genotype at this variant position is at least denovo_nonref_allele_min_father_coverage.

  • The coverage of the mother's genotype at this variant position is at least denovo_nonref_allele_min_mother_coverage.

Note: The coverage parameters help avoid false-positive calls that might arise simply because the sequencing coverage is inadequate to call an accurate genotype. Without coverage information, the absence of a variant call for a parent is only absence of evidence, and we cannot exactly determine that the allele for the proband is de novo. To establish evidence of absence, we require that the parents be covered well enough that variants are called if actually present. Therefore we require that the position in both parents meets a coverage threshold.