Clinical Next-Generation Sequencing Database

Clinical NGS database employed a statistical approach to variant pathogenicity classification that uses the odds ratio for comparisons between the case and the control comparison in each inheritance mode (families with apparently autosomal dominant inheritance vs. control, and families with apparently autosomal recessive inheritance vs. control).

 

Most of the pathogenic variants for autosomal recessive inherited disorders are preferentially observed among families with apparently autosomal recessive inheritance or sporadic cases and are seldom identified among families with apparently autosomal dominant inheritance. The occurrence of these variants identified in families with apparently autosomal dominant inheritance was considered to show the same prevalence as the carrier frequencies in the control population.

 

In contrast, pathogenic variants for autosomal dominant inherited diseases should be mainly identified among families with apparently autosomal dominant inheritance and not usually identified from families with apparently autosomal recessive inheritance or sporadic cases. The occurrence of an autosomal dominant inherited pathogenic variant among families with apparently autosomal recessive inheritance or sporadic cases was considered a de novo mutation or the incomplete penetrance of the variant.

 

Clinical NGS database automatically calculated inheritance mode specific odds ratio for the comparison between the case and the control with 95% confidence interval and p-value.