Introduction

Recent advancement of next-generation sequencing (NGS) has made sequencing of whole genome or exome (WGS/WES) at single-base resolution with high speed and low cost. As a new clinical testing tool, WGS/WES of proband and affected family has been widely used to identify genetic aberrations underlying Mendelian or complex genetic disorders. However, more than tens of thousands of sequence variants could be detected by WGS/WES typically, and to efficiently and accurately identify the one or few acutal pathogenic sequence variants among the majority of un-relevant ones is complicated and challenging. It was reported that different types of function-related information on nucleotide and gene level obtained from public databses, software tool predictions and literatures should be utilized to prioritize for pathogenic sequence variants. Importantly, the American College of Medical Genetics and Genomics (ACMG) has recently released its new guideline for sequence variants interpretations and classification as for pathogenicity based on comprehensive evidences. Here we have developed an easy-to-use and freely accessible webserver named mirVAFC for pathogenic sequence variants prioritizations according to the ACMG guidelines. The mirVAFC was mainly developped for clinical exome sequencing (CES) variants data analysis for single proband or multiple family members affected by inherited disorders.

Main functionalities:

Process overview:

The mirVAFC accepts sequencing variants file (in VCF format) produced by WGS/WES for single individual or multiple family members and disease names or corresponding IDs from OMIM and HPO databases as required input. Pedigree file to indicate family relationship, sex and affected status should also be supplied for family data analysis. Sequencing variants annotation, filtering, classification and prioritization will be performed sequentially by mirVAFC. The overall work flow is depicted as bellow:

workflow


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