Clinical Genetic Databases: ClinVar, ACMG Clinical Practice Guidelines

This chapter covers clinical genetics databases, which include databases explicitly focused on clinically important genetic variants, including the National Institutes of Health’s Clinical Variants database (ClinVar), the American College of Medical Genetics (ACMG)’s Clinical Practice Guidelines around actionable variants, the pharmacogenomic knowledge base (PharmGKB) and pharmacogenomics variants, and the Online Mendelian Inheritance in Man (OMIM). We also cover databases that are important for understanding variants in general, which have relevance when understanding the clinical actionability of a variant; these databases include the Genome Aggregation Database (GNOMAD) browser for determining prevalence of variants in different ancestry groups and ethnic populations (e.g., Amish); the encyclopedia of single-nucleotide polymorphisms (SNPs) called SNPedia, and the GWAS Catalog. We will also cover how to link individual users or participants genetics; direct-to-consumer (DTC) genetic results to ClinVar and how to evaluate the participant’s zygosity for clinically pathogenic variants as reported by ClinVar. We also describe additional ways for establishing strength and support for a variants clinical importance using linkage with clinical practice guidelines, literature support, and the number of laboratories reporting consistent results. This additional layer of support can help identify potential biases in the data. We will also cover how DTC companies such as 23andme report their pathogenic variants versus how they are covered in ClinVar and how this variability is mainly due to the target audience: general public (23andme) versus researchers and clinical genetics (ClinVar). After reading this chapter, you should be able to confidently answer the following questions: