Applying ACMG Guidelines to Analyze Germline Diseases
The clinical interpretation of variants in Next-Gen Sequencing is a quickly evolving field. While the body of knowledge is growing exponentially, experts have to derive sound, clinical decisions leveraging an ever-expanding set of specialty databases, clinical publications, and algorithms that are designed to predict the impact of specific variants in the resulting protein.
The specific steps and considerations that need to be considered are defined by the American College of Medical Genetics and Genomics. The guidelines for the interpretation of sequenced variants were published in 2015 with an addendum for loss of function variants added in 2018. A second set of guidelines for interpreting Copy Number Variants (CNVs) was published in 2020.
In this eBook, I have summarized the key concepts of these guidelines, including:
- What defines a pathogenic and respectively a benign variant
- Scoring mechanisms that allow us to classify a variant clinically
- A few interesting cases of variants and their classifications
Dr. Andreas Scherer is CEO of Golden Helix. The company has been delivering industry-leading bioinformatics solutions for the advancement of life science research and translational medicine for over a decade. Its innovative technologies and analytic services empower scientists and healthcare professionals at all levels to derive meaning from the rapidly increasing volumes of genomic data produced from next-generation sequencing. With its solutions, hundreds of the world’s hospitals and testing labs are able to harness the full potential of genomics to identify the cause of disease, develop genomic diagnostics, and advance the quest for personalized medicine. Golden Helix products and services have been cited in thousands of peer-reviewed publications. Golden Helix is also on the Inc 5000 list of the fastest-growing private companies in the US.
He is also Managing Partner of Salto Partners, Inc., Inc., a management consulting firm headquartered in Nevada. He has extensive experience successfully managing growth as well as orchestrating complex turnaround situations. His company, Salto Partners, advises on business strategy, financing, sales, and operations. Clients are operating in the high-tech and life sciences space.
Dr. Scherer holds a Ph.D. in computer science from the University of Hagen, Germany, and a Master of Computer Science from the University of Dortmund, Germany. He is author and co-author of over 20 international publications and has written books on project management, the Internet, and artificial intelligence. His latest book, “Be Fast Or Be Gone”, is a prizewinner in the 2012 Eric Hoffer Book Awards competition, and has been named a finalist in the 2012 Next Generation Indie Book Awards!