Copy number variation (CNV) identification, interpretation, and database from Brazilian patients

Author(s)

Victória Cabral Silveira Monteiro de Godoy ^[1] ; Fernanda Teixeira Bellucco ^[2] ; Mileny Colovati ^[3] ; Hélio Rodrigues de Oliveira-Junior ^[4] ; Mariana Moysés-Oliveira ^[5] ; Maria Isabel Melaragno ^[6]

Affiliation

^[1] Universidade Federal de São Paulo. Departamento de Morfologia e Genética. Disciplina de Genética - Brasil

^[2] Universidade Federal de São Paulo. Departamento de Morfologia e Genética. Disciplina de Genética - Brasil

^[3] Universidade Federal de São Paulo. Departamento de Morfologia e Genética. Disciplina de Genética - Brasil

^[4] Universidade Federal de São Paulo. Departamento de Morfologia e Genética. Disciplina de Genética - Brasil

^[5] Universidade Federal de São Paulo. Departamento de Morfologia e Genética. Disciplina de Genética - Brasil

^[6] Universidade Federal de São Paulo. Departamento de Morfologia e Genética. Disciplina de Genética - Brasil

• Document type: Journal article
• Source: GENETICS AND MOLECULAR BIOLOGY; v. 43, n. 4 2020-11-13.

Abstract

Abstract Copy number variations (CNVs) constitute an important class of variation in the human genome and the interpretation of their pathogenicity considering different frequencies across populations is still a challenge for geneticists. Since the CNV databases are predominantly composed of European and non-admixed individuals, and Brazilian genetic constitution is admixed and ethnically diverse, diagnostic screenings on Brazilian variants are greatly difficulted by the lack of populational references. We analyzed a clinical sample of 268 Brazilian individuals, including patients with neurodevelopment disorders and/or congenital malformations. The pathogenicity of CNVs was classified according to their gene content and overlap with known benign and pathogenic variants. A total of 1,504 autosomal CNVs (1,207 gains and 297 losses) were classified as benign (92.9%), likely benign (1.6%), VUS (2.6%), likely pathogenic (0.2%) and pathogenic (2.7%). Some of the CNVs were recurrent and with frequency increased in our sample, when compared to populational open resources of structural variants: 14q32.33, 22q11.22, 1q21.1, and 1p36.32 gains. Thus, these highly recurrent CNVs classified as likely benign or VUS were considered non-pathogenic in our Brazilian sample. This study shows the relevance of introducing CNV data from diverse cohorts to improve on the interpretation of clinical impact of genomic variations. (AU)

• FAPESP's process: 14/11572-8 - Chromosomal rearrangements and their relevance in the etiology of genetic disorders: cytogenomic and molecular investigation
• Grantee: Maria Isabel de Souza Aranha Melaragno
• Support Opportunities: Research Projects - Thematic Grants