Prevalence and properties of intragenic copy-number variation in Mendelian disease genes.

ABSTRACT:

Purpose

We investigated the frequencies and characteristics of intragenic copy-number variants (CNVs) in a deep sampling of disease genes associated with monogenic disorders.

Methods

Subsets of 1507 genes were tested using next-generation sequencing to simultaneously detect sequence variants and CNVs in >143,000 individuals referred for genetic testing. We analyzed CNVs in gene panels for hereditary cancer syndromes and cardiovascular, neurological, or pediatric disorders.

Results

Our analysis identified 2844 intragenic CNVs in 384 clinically tested genes. CNVs were observed in 1.9% of the entire cohort but in a disproportionately high fraction (9.8%) of individuals with a clinically significant result. CNVs accounted for 4.7-35% of pathogenic variants, depending on c

SUBMITTER: Truty R 

PROVIDER: S-EPMC6752305 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature