> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/emedgene/emedgene-analyze-manual/variant_page/evidence_section/acmg_snv_classification_wizard.md). # ACMG SNV Classification wizard The **ACMG SNV Classification wizard** is located in the [**Evidence tab**](/emedgene/emedgene-analyze-manual/variant_page/evidence_section.md) of the [**Variant page**](/emedgene/emedgene-analyze-manual/variant_page/variant_page.md). It facilitates classification of variant pathogenicity through the [automation of 26 out of 28 ACMG criteria](/emedgene/emedgene-analyze-manual/variant_page/evidence_section/logic_behind_acmg_classification_of_snvs.md) and enabling manual review and editing of the tags presented as interactive buttons. 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). ![](/files/PfI0M5u4ZxKqMC8x2LlV) The ACMG SNV Classification wizard includes a pathogenicity bar that visually represents the [pathogenicity score](/emedgene/emedgene-analyze-manual/variant_page/evidence_section/logic_behind_acmg_classification_of_snvs.md). The wizard is available for **tagged SNVs in disease-associated genes** and displays a visual **pathogenicity bar** summarizing the cumulative pathogenicity score. ![](/files/rQNQ13bhN32u38U1XHJD) The wizard is available for tagged sequence variants in disease-associated genes. The results of the classification are also highlighted in the [**Clinical Significance tab**](/emedgene/emedgene-analyze-manual/variant_page/clinical_significance_section.md) of the [**Variant page**](/emedgene/emedgene-analyze-manual/variant_page/variant_page.md). Unlike the wizard, automatically assigned criteria and resulting variant class are shown in the [**Clinical Significance tab**](/emedgene/emedgene-analyze-manual/variant_page/clinical_significance_section.md) for all variants in disease-associated genes, regardless of their [tagging](/emedgene/emedgene-analyze-manual/variant_page/variant_tagging_widget.md) status. ## How to 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). ![](/files/qIstp8GakVFqLY3FhSsA) 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). ![](/files/SowivdmsdtGXUzwJtImC) 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. ![](/files/cFapMBOZrtvIyN9kXknF) ![](/files/XbnC0xOQZGCkDj2MzR0Y) 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. {% hint style="info" %} ### Tips * Always **review tag strengths** before finalizing, especially for borderline LP/P classifications. * Check for **automatic exclusions** (PP5, BP6) so you understand why they don’t contribute to scoring. * Avoid overriding **PM2**, **PM1**, or **PP3** without justification — the system’s defaults are based on published recommendations. * Use the **activity log** to track and audit all manual modifications. * Pay attention to **real-time warnings** — they’re designed to prevent misclassification due to known interpretation pitfalls. {% endhint %} ## Curate annotation ACMG tags imported from **Curate** are indicated by a Curate icon. **Curate** annotation includes tag status, strength, answered questions, and notes. The system displays the [ACMG classification stored in **Curate**](/emedgene/emedgene-curate-manual/curate_variants/curate_variant_page.md#acmg-classification-card) when all of the following are true: * The variant has an entry in **Curate** * The variant is a SNV * The variant is tagged by the **AI Shortlist** in the current **Analyze** case * The ACMG schema version in **Curate** matches the schema active in **Analyze** ### ACMG schema version discrepancy between Analyze and Curate The ACMG schema defines how evidence is interpreted and how pathogenicity is determined. It is periodically updated to incorporate new ClinGen/ACMG recommendations and platform logic improvements. If a variant in **Curate** was classified using an older schema than the one currently active in **Analyze**: * The system applies the current schema active in **Analyze**. * **Curate** annotation is not displayed. * A warning appears in the ACMG SNV Classification wizard. Whenever a mismatch warning appears: 1. Re‑evaluate the evidence using the current schema. 2. Select **Update Curate** to update the classification and synchronize schema versions for the variant. ## Disease source used in ACMG evaluation When a gene–disease association is available from multiple databases (for example: OMIM, CGD, Orphanet etc.), the **Variant page** and **Gene related diseases** card display all available disease sources.\ However, **ACMG inheritance-based rules use only the OMIM disease to determine the inheritance mode.** ## 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)](https://pubmed.ncbi.nlm.nih.gov/32906214/): PM1, PM3, PP2, PP5, BP1, BP3, BP6. ![](/files/HiUeAB6RM45OHwMiti0C) ## Learn more
Logic behind ACMG classification of SNVsUnderstand ACMG score calculation, classification thresholds, and combination rules for SNVs.:arrow-up-right-from-square: Learn more
Individual ACMG criteria evaluationReview how each ACMG criterion is evaluated and which criteria require manual input.:arrow-up-right-from-square: Learn more
ACMG CNV Classification wizardSee how ACMG classification works for CNVs and how to review CNV-specific evidence.:arrow-up-right-from-square: Learn more
Evidence tabReturn to the Evidence tab overview for related interpretation workflows and tools.:arrow-up-right-from-square: Learn more
--- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com. ## Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. Perform an HTTP GET request on the current page URL with the `ask` query parameter: ``` GET https://help.connected.illumina.com/emedgene/emedgene-analyze-manual/variant_page/evidence_section/acmg_snv_classification_wizard.md?ask= ``` The question should be specific, self-contained, and written in natural language. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.