Copy-number variants in clinical genome sequencing: deployment and interpretation for rare and undiagnosed disease.

ABSTRACT:

Purpose

Current diagnostic testing for genetic disorders involves serial use of specialized assays spanning multiple technologies. In principle, genome sequencing (GS) can detect all genomic pathogenic variant types on a single platform. Here we evaluate copy-number variant (CNV) calling as part of a clinically accredited GS test.

Methods

We performed analytical validation of CNV calling on 17 reference samples, compared the sensitivity of GS-based variants with those from a clinical microarray, and set a bound on precision using orthogonal technologies. We developed a protocol for family-based analysis of GS-based CNV calls, and deployed this across a clinical cohort of 79 rare and undiagnosed cases.

Results

We found that CNV calls from GS are at least as sensitive a

SUBMITTER: Gross AM 

PROVIDER: S-EPMC6752263 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature