Data/hora: 02/06/2024 08:27:22

Provedor de dados: 	74	
País: 	Brazil	
Título: 	Determining the pathogenicity of CFTR missense variants: Multiple comparisons of in silico predictors and variant annotation databases	
Autores: 	Michels,Marcus; Matte,Ursula; Fraga,Lucas Rosa; Mancuso,Aline Castello Branco; Ligabue-Braun,Rodrigo; Berneira,Elias Figueroa Rodrigues; Siebert,Marina; Sanseverino,Maria Teresa Vieira.	
Data: 	2019-09-01	
Ano: 	2019	
Palavras-chave: 	CFTR; Missense variant; Prediction; Bioinformatics; Cystic fibrosis.	
Resumo: 	Abstract Pathogenic variants in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for cystic fibrosis (CF), the commonest monogenic autosomal recessive disease, and CFTR-related disorders in infants and youth. Diagnosis of such diseases relies on clinical, functional, and molecular studies. To date, over 2,000 variants have been described on CFTR (~40% missense). Since few of them have confirmed pathogenicity, in silico analysis could help molecular diagnosis and genetic counseling. Here, the pathogenicity of 779 CFTR missense variants was predicted by consensus predictor PredictSNP and compared to annotations on CFTR2 and ClinVar. Sensitivity and specificity analysis was divided into modeling and validation phases using just variants annotated on CFTR2 and/or ClinVar that were not in the validation datasets of the analyzed predictors. After validation phase, MAPP and PhDSNP achieved maximum specificity but low sensitivity. Otherwise, SNAP had maximum sensitivity but null specificity. PredictSNP, PolyPhen-1, PolyPhen-2, SIFT, nsSNPAnalyzer had either low sensitivity or specificity, or both. Results showed that most predictors were not reliable when analyzing CFTR missense variants, ratifying the importance of clinical information when asserting the pathogenicity of CFTR missense variants. Our results should contribute to clarify decision making when classifying the pathogenicity of CFTR missense variants.	
Tipo: 	Info:eu-repo/semantics/article	
Idioma: 	Inglês	
Identificador: 	http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000400560	
Editor: 	Sociedade Brasileira de Genética	
Relação: 	10.1590/1678-4685-gmb-2018-0148	
Formato: 	text/html	
Fonte: 	Genetics and Molecular Biology  v.42 n.3 2019	
Fonte: 	info:eu-repo/semantics/openAccess