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

• Autor(a) principal: Godoy,Victória Cabral Silveira Monteiro de
• Data de Publicação: 2020
• Outros Autores: Bellucco,Fernanda Teixeira, Colovati,Mileny, Oliveira-Junior,Hélio Rodrigues de, Moysés-Oliveira,Mariana, Melaragno,Maria Isabel
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Genetics and Molecular Biology
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572020000600103
• topic: CNV; copy number variation; database; CNV classification

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.