Comprehensive analysis of ADA2 genetic variants and estimation of carrier frequency driven by a function-based approach.

ABSTRACT:

Background

Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by deleterious ADA2 variants. The frequency of these variants in the general population, and hence the expected disease prevalence, remain unknown.

Objective

We aimed to characterize the functional impact and carrier frequency of ADA2 variants.

Methods

We performed functional studies and in silico analysis on 163 ADA2 variants, including DADA2-associated variants and population variants identified in the Genome Aggregation Database. We estimated the carrier rate using the aggregate frequency of deleterious variants.

Results

Functional studies of ADA2 variants revealed that 77 (91%) of 85 of DADA2-associated variants reduced ADA2 enzymatic function by >75%. Analysis of 1

SUBMITTER: Jee H 

PROVIDER: S-EPMC8591146 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature