Applying AMP Guidelines to Analyze Somatic Variants
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 benign variant respectively, and everything in between
- Scoring mechanisms that allow us to classify a variant clinically
- A few interesting cases of variants and their classifications
This eBook should be read in the context of two others that appeared in our series. The first one is called “Genetic Testing for Cancer”. It describes the general background of NGS-based tests in this field. It outlines, how we zero in on variants and CNVs of interest with the help of a state-of-the-art secondary and tertiary analytics pipeline.
The second eBook is called “Clinical Variant Interpretation – Applying ACMG guidelines to Analyze Germline Diseases”. It is relevant for Clinicians who need to report on hereditary cancer types such as BRCA1 and BRCA2. This topic is also covered briefly in this eBook.
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 two decades. Its innovative technologies and analytic services empower clinicians and scientists at all levels to derive meaning from the rapidly increasing volumes of genomic data produced from next-generation sequencing and micro-arrays. With its solutions, hundreds of the world’s hospitals, testing labs, academic research organizations and governments 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.
He is also Managing Partner of Salto Partners, a management consulting firm headquartered in the DC metro area. He has extensive experience successfully managing growth as well as orchestrating complex turnaround situations.
Dr. Scherer holds a PhD 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!