Challenging popular tools for the annotation of genetic variations with a real case, pathogenic mutations of lysosomal alpha-galactosidase.

ABSTRACT:

Background

Severity gradation of missense mutations is a big challenge for exome annotation. Predictors of deleteriousness that are most frequently used to filter variants found by next generation sequencing, produce qualitative predictions, but also numerical scores. It has never been tested if these scores correlate with disease severity.

Results

wANNOVAR, a popular tool that can generate several different types of deleteriousness-prediction scores, was tested on Fabry disease. This pathology, which is caused by a deficit of lysosomal alpha-galactosidase, has a very large genotypic and phenotypic spectrum and offers the possibility of associating a quantitative measure of the damage caused by mutations to the functioning of the enzyme in the cells. Some predictors, and in

SUBMITTER: Cimmaruta C 

PROVIDER: S-EPMC6266955 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature