# ACMG criteria and classification

NOTE

This documentation is a work in progress and is not currently up to date.

Please contact developers for more details.

# ACMG rules engine

Rules for suggested ACMG criteria are defined in JSON format in:

  • File: /src/rule_engine/mapping_rules.py
  • Key: rules

See /src/rule_engine/README for details.

# User group rules

User group-specific ACMG value rules. See /src/vardb/testdata/usergroups.json for examples.

  • File: usergroups.json (see user groups)
  • Key: config.acmg

The following subkeys define thresholds and values that act as input for the ACMG rules engine, for the given user group:

Subkey Explanation Values
frequency.thresholds * The population frequency threshold for ACMG criteria BA1 (hi_freq_cutoff) and BS1 (lo_freq_cutoff). 0-1
frequency.num_thresholds * The minimum "allele number" (observed chromosomes at a given locus) for each sub-population. [integer]
disease_mode Whether only missense (MISS) or loss of function (LOF) mutations, or both (ANY), are expected to cause disease. MISS / LOF / ANY (default)
last_exon_important Whether the last exon is important (LEI) or not (LENI). LEI (default) / LENI

* Similar to filter frequency thresholds, with possibilities for separation of dataset groups and inheritance modes.

# Gene-specific overrides

To define rules for given genes only (within a user group), place the above subkeys within the config.acmg.genes key, providing a HGNC ID for each gene the rules should apply to.

In addition, the subkey comment can be defined, specifying information relevant to evaluation of more/all variants in a gene as free text.

# ACMG descriptions

Short (short_criteria) and long (criteria) descriptions and any notes for each ACMG criterion and REQ (shown in UI pop-ups) are given in:

  • File: /src/api/config/acmgconfig.py
  • Key: acmgconfig["explanation"]

For REQs, you can also define which ACMG criteria the REQ relates to in this file, using the key sources.

# Classification

Sort order and time to outdated (how long an interpretation is considered valid) for clinical classifications is given in:

  • File: ella_config.yml (set by ELLA_CONFIG env variable)
  • Key: classification.options

See /example_config.yml for examples.

Last Updated: 1/17/2020, 3:30:26 PM