Frequency of sex chromosome involvement in a large cohort of subjects with two copy number variants (CNVs).

Abstract

Copy number variants (CNVs) are a common finding in the clinical setting and contribute to both genetic variation and disease. Studies have described the accumulation of multiple CNVs as a disease modifying mechanism. While it has been described how additional CNVs may play a role in phenotype, in which ways and to what extent sex chromosomes are involved in dual CNV scenario has not been fully defined. To describe the distribution of CNVs, a secondary data analysis using the DECIPHER database on 2,273 de-identified individuals with two CNVs was performed. CNVs were designated larger and secondary based on size and characteristics. We found that the X chromosome was observed to be the most common chromosome involved in secondary CNVs. Further analysis showed CNVs on the sex chromosome have significant differences compared to autosomes when comparing median size (p=0.013), pathogenicity groups (p<0.001), and variant classification (p=0.001). Lastly, we identified chromosome combinations for larger and secondary CNVs, and observed the plurality of secondary CNVs fell in the same chromosome as the larger. The observations of this study provide additional information on sex chromosome CNV involvement in a variety of indications.