Sherloc is a logical framework for evaluating genetic evidence and combining this evidence into a consistent and reproducible classification of both genes and variants. Importantly, this framework is based on guidelines for the Interpretation of Sequence Variants (ISV) published by a joint ACMG and AMP working group in 2015. Through an iterative and experiential process we started with 33 ISV rules, refined these to provide greater clarity, and introduced more than 100 additional rules to capture a wider variety of edge cases and exceptions routinely encountered during clinical genetic testing. The outcome of these changes is a more reliable, scalable and efficient variant interpretation process. If you would like to hear more about the specific improvements we’ve made and how Sherloc compares to the ACMG-AMP ISV guidelines, please see the invited commentary in Genetics In Medicine or watch our Sherloc webinar.
For a more detailed description of the Sherloc framework and evidence criteria used to interpret sequence variants see the manuscript published in Genetics in Medicine.