Front Cover: The cover image is based on the Editorial Introduction Human mutation special issue on “variant effect prediction” by Ales Maver et al., https://doi.org/10.1002/humu.24429.

The Ensembl Variant Effect Predictor (VEP) is a freely available, open-source tool for the annotation and prioritization of genomic variants. It maps variants to functionally relevant genomic regions and predicts their consequence. In this tutorial, we explain how to use the Ensembl VEP web interface and describe the available annotation options, including reference population frequency data, phenotype associations, variant citation data, and pathogenicity predictors.

The new UCSC Recommended Track Sets are designed to facilitate the interpretation of variants in the genome, offering quick access to relevant and appropriately configured tracks, allowing visualization and easy comparison of data from multiple sources, and support researches in understanding the relationship between genetic variants and human disease in the course of testing patient specimens. “Supporting Information” is included.

Reference population databases are critical in the interpretation of genomic variation for diagnosing rare disease, and supports the discovery of new disease–gene relationships. This review provides guidance for using the Genome Aggregation Database (gnomAD) browser and key features like allele frequency, per-base expression levels, constraint scores, and variant co-occurrence, for variant and gene interpretation in clinical and research analysis.

Lessons learned from performing clinical exome sequencing for over 10 years.

The purpose of these guidelines is to provide a formal integration of RNA phenotypes into the American College of Medical Genetics and Genomics and the Association for Molecular Pathology framework as functional evidence. These recommendations were also designed to serve as an educational resource for clinical laboratory geneticists to facilitate the clinical implementation of RNA-seq (RNA-sequencing).

A clinician's checklist to judge gene-disease relationships for ultra-rare disease.

Rett/AS VCEP variant interpretation guidelines for MECP2, CDKL5, FOXG1, UBE3A, SLC9A6, and TCF4.