ACMG Guidelines are not a definitive variant classification program and “following” the guidelines does not quantify a lab’s interpretive accuracy.
“[L]aboratories should not simply use currently available disease-specific databases for directly filtering variants to determine which will be reported as disease causing. Few, if any, variant databases are curated to a clinical grade with strict, evidence-based consensus assessment of supporting data. It is well known that many databases contain misclassified variants, particularly benign variation misclassified as disease causing.”
Joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, May 2015.