ACMG classification support

In the Knowledge Base, Moon offers support for SNV variant classification based on the ACMG guidelines (Richards et al., 2015).

When opening a variant on the KB overview page, the ACMG criteria section first lists a summary of all criteria that have been selected for the variant. Clicking the arrow next to this summary of criteria will expand this section to show the overview of all ACMG criteria, grouped by properties that are covered by the ACMG classification system (Segregation, Disorder, Effect, Computational and functional, Gene region, Frequency). These can be manually selected (by clicking them) when editing a KB variant. ACMG criteria are not automatically applied by the software, and by default, all criteria are unselected.

Open

Selected criteria are highlighted in red or green, depending on the Pathogenic or Benign contribution of the criterium. Unselected criteria only have a coloured border.

Hovering over each criterium shows a tooltip in which the criterium info is displayed. Additionally, for criteria for which more extended or refined rules have been published or recommended since the original publication, a link is provided to open the relevant resources.

Clicking a criterium will select it with the predefined strength. The dropdown menu in each criterium allows to you modify the criterium strength to a level of choice (VS = very strong; S = strong; M = moderate P = supporting).

At the top right of the ACMG section, the classification of the variant is displayed based on the combination of criteria and strengths that were manually selected. Clicking the ‘Confirm as’ button will change the KB classification of the variant to the proposed classification based on the criteria. By default, if no criteria are selected, the proposed classification is VUS.