6. Dominant InheritedΒΆ

If you click on the 4 at the bottom of the Dominant Inherited filter container, it will display those variants that have passed the filter restrictions for this inheritance pattern in the variant table.

Dominant Inherited

Figure 6-1: Dominant inherited filter logic.

The Dominant Inherited filter logic is based on Mendel Error, Zygosity of the parents and proband, Gene Inheritance, and the Auto Classification from the ACMG Sample Classifier. The unique filter card that is used for this chain was created based on output from our Genotype Zygosity algorithm. Genotype Zygosity is already in the samples field of the variant table but if absent can be found under the Add>Computed Data>Genotype Zygosity. If you expand the Either Parent is Heterozygous card, it will show you a more detailed filter logic. Specifically, this card is filtering for variants that are heterozygous in the father and reference or missing in the mother, or heterozygous in the mother and reference or missing in the father.

Parent zygosity

Figure 6-2: Variants present in the mother or father that are reference or missing in the spouse.

The next filter card identifies transmitted variants that are heterozygous for the proband (Current) as well as Dominant for the gene inheritance pattern. The gene inheritance pattern comes from the ACMG samples classifier but is based on the gene inheritance according to OMIM. Furthermore, Likely Pathogenic, Pathogenic or VUS/Weak Pathogenic Variants from the ACMG Auto Classification are selected. Together this filter logic identified 4 variants that were transferred from either the mother or the father to the proband. You can also click on these dominant inherited variants in the variant table and open Genome Browse to visualize which parent transferred the variant to the proband. For example, if you click on the row that contains the T/C variant at chromosome and position 7:151935853, you will see in Genome Browse that the allele is inherited from the father. Once finished viewing, reopen the Filter Variant tab to investigate the next filter logic: Recessive Homozygous variants.

ACMG options dialog

Figure 6-3: Genome Browse view of dominant iherited variants.