Segregating variants analysis

The segregating variants analysis falls in the category of algorithmic filters that can be performed on Family trio analyses.

 

trio

 

The Segregating Variants algorithmic filter can be found in the Algorithmic Filter Analysis launch page. 

It is a parameterizable algorithmic filter with the following optios:

Segregating dominant variants

Variants annotated as pathogenic, likely pathogenic, or of unknown function (but only if one of the strong pathogenic ACMG rules has fired for this variant) that are present (in any zygosity) in all affected samples and absent from all healthy samples. Select the "Strong VUS" option.

Segregating recessive variants

Variants annotated as pathogenic, likely pathogenic, or of unknown function (but only if one of the strong pathogenic ACMG rules has fired for this variant) that are homozygous in all affected samples but heterozygous or absent from all healthy samples. Select the "Segregating recessive" option.

Compound heterozygous segregating

Variants present (in any zygosity) in all affected samples and absent from all healthy samples and it will also find possible segregating compound heterozygous variants: those variants annotated as pathogenic, likely pathogenic, or of unknown function that are found in genes where all affected samples have at least two so annotated heterozygous variants. Select the "Compound heterozygous segregating" option.

This option cannot be used in combination with the Segregating recessive option

Running the analysis with multiple affected samples

Please note that this filter is not specifically designed for family trios, but for general multi-sample (e.g. cohort) analyses. When running it with multiple affected samples, it will look for variants that are homozygous in all affected samples and absent or heterozygous in all healthy samples. The segregating variants (dominant) filter will look for variants that are present (het or hom) in all affected samples and absent in all healthy samples.