wInterVar: a web server for clinical interpretation of non-synonymous variants by InterVar.
In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published updated standards and guidelines for the clinical interpretation of sequence variants with respect to human diseases on the basis of 28 criteria. However, variability between individual interpreters can be extensive because of reasons such as the different understandings of these guidelines and the lack of standard algorithms for implementing them, yet computational tools for semi-automated variant interpretation are not available. To address these problems, we propose a suite of methods for implementing these criteria and have developed a tool called InterVar to help human reviewers interpret the clinical significance of variants. InterVar can take a pre-annotated or VCF file as input and generate automated interpretation on 18 criteria. Furthermore, we have developed a companion web server, wInterVar, to enable user-friendly variant interpretation with an automated interpretation step and a manual adjustment step. These tools are especially useful for addressing severe congenital or very early-onset developmental disorders with high penetrance. Using results from a few published sequencing studies, we demonstrate the utility of InterVar in significantly reducing the time to interpret the clinical significance of sequence variants.
wInterVar is a web implementation of InterVar so that users can use an online web server to perform interpretation on individual variants without using command-line tools. The wInterVar server has two steps for assessing and adjusting the clinical significance of variants: users first input a variant to obtain pre-computed, automated interpretation (Figure A below). After reviewing the results of automated interpretation, users can then click the “adjust” button to perform the manual adjustment step by selecting and de-selecting appropriate criteria according to additional information and domain knowledge. The wInterVar server will then perform the final interpretation with the two-step procedure (Figure B below).
wInterVar is available at http://wintervar.wglab.org/.
Quan Li and Kai Wang. InterVar: Clinical interpretation of genetic variants by ACMG-AMP 2015 guideline. American Journal of Human Genetics, 100(2):267-280, 2017