ACMG SNV Classification wizard
Where can I review and edit the ACMG Classification of a SNV?
The ACMG SNV Classification Wizard is located in the Evidence section of the Variant Page and is designed to guide users through the interpretation of single nucleotide variants (SNVs) using the ACMG/AMP framework. It automates 26 out of 28 ACMG criteria, with PS4 requiring full manual entry and BS2 partially automated (50% manual).

The ACMG SNV Classification wizard includes a pathogenicity bar that visually represents the pathogenicity score.
The wizard is available for tagged SNVs in disease-associated genes and displays a visual pathogenicity bar summarizing the cumulative pathogenicity score.

The results of the classification are also highlighted in the Clinical Significance section of the Variant page. Unlike the wizard, automatically assigned criteria and resulting variant class are shown in the Clinical Significance section for all variants in disease-associated genes, regardless of their tagging status.
How do I review and edit the ACMG Classification of a SNV?
Each ACMG tag is represented by an interactive button including a checkbox for selection (1), the criterion name (2) and evidence strength indicator (3).

Pathogenic criteria are represented by red boxes, while benign criteria boxes are colored green. Each ACMG criterion has three possible states:
Neutral (1) - represented by an empty checkbox. Criterion requires further investigation.
Negative (2) - represented by a cross. Criterion is not applicable.
Positive (3) - represented by a tick and dark color. Criterion is applicable.
Each ACMG tag can be manually checked, unchecked, or set to an undefined state by clicking the interactive button's checkbox element.
To examine in detail or modify the underlying evidence for the particular ACMG tag, select it by clicking on the tag name. The button becomes flood-filled (b), as opposed to it's original, non-selected, state (a).

Upon selection, a description of the criterion and its underlying evidence emerges below. Yes and No radio buttons accompany each piece of evidence. The tag can be assigned if Yes has been selected for all the underlying conditions.


You may modify evidence strength in the Strength dropdown (Stand Alone, Very Strong, Strong, Moderate, Supporting), which will impact both the pathogenicity class and score calculations.
Notes can be added to any tag, and changes are saved using the Save button.
After you've modified ACMG classification, you can either save manual changes by pressing the Save button or reset via Revert manual changes. Keep in mind that after saving your edits, Revert manual changes will become unavailable.
Warnings for ACMG tag schema versions
ACMG classifications rely on a defined ACMG tag schema, which is periodically updated to reflect new ClinGen/ACMG recommendations or platform logic improvements. To ensure classification accuracy, schema versioning is now tracked independently from the overall variant analysis engine.
When opening a case in Analyze, the system compares:
The ACMG schema version currently applied in the case analysis
The ACMG schema version used when the variant was curated in Curate
If the curated schema is older than the current schema:
Curated ACMG tags will not be applied in Analyze
The system reapplies the current schema’s criteria
A warning appears:
WARNING:
Curate: ACMG tags were curated using an outdated schema and weren't applied in the current analysis. Update Curate to align schema.
You can synchronize schemas by clicking Update Curate on the variant. This updates the variant’s ACMG schema version in Curate to match Analyze, and the updated classification is saved like any other variant update.
Warning: If you proceed without updating, the variant in Analyze will not reflect the ACMG tags curated earlier in Curate, which may lead to classification discrepancies.
ACMG classification of mtDNA variants
The ACMG SNV Classification wizard is available for ACMG classification of tagged mtDNA variants. To classify an mtDNA variant, please manually assign the relevant criteria; the resulting ACMG classification will be calculated automatically.
Seven criteria have been removed in compliance with Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation (2020): PM1, PM3, PP2, PP5, BP1, BP3, BP6.

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