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
  • User group rules
• ACMG descriptions
• Classification

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 usergroups.json (opens new window) 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 how long an interpretation should be considered valid (outdated_after_days) for clinical classifications is given in:

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

See example_config.yml (opens new window) for examples.