Evidence interpretation rules
This document defines the canonical rules used to translate observed genomic data flags into binary evidence indicators under the Qualifying Evidence Matrix. It applies to trio-based whole-genome sequencing for rare Mendelian disease analysis.
Technical information
- Resource name: Evidence interpretation rules for trio-based rare disease screening
- File name: evidence_interpretation_rules_e7af8e5dc03accac17b690d244995afa.html
- Description: Canonical rule set defining how verifiable evidence from parent–child trio whole-genome sequencing is interpreted under the Qualifying Evidence Matrix.
- Stable URL: Link via swissgenomicsassociation
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MD5 checksum:
e7af8e5dc03accac17b690d244995afa - Intended scope: Trio-based whole-genome sequencing for rare Mendelian disease screening
How to read this table
- Rule name, Meaning, and Flag describe how available genetic and family data are interpreted to assess support for a proposed disease-causing variant.
- Each rule can return one of three flag values: TRUE, FALSE, or NA. Under the Qualifying Evidence Matrix standard, only FALSE outcomes contribute supporting evidence.
- The Evidence column shows the final outcome of each rule. A tick (✓) indicates confirmable supporting evidence is present. A cross (✕) indicates contradictory or unavailable evidence.
| Rule name | Meaning | Flag | Evidence |
|---|---|---|---|
| parent gt unavailable | Parental genetic data are missing, so inheritance cannot be assessed | TRUE | ✕ No |
| parent gt unavailable | Parental genetic data are available and inheritance can be evaluated | FALSE | ✓ Yes |
| parent gt unavailable | It is unknown whether parental genetic data are available | NA | ✕ No |
| parent gt mechanistically inconsistent ar | Parental results rule out an autosomal recessive explanation | TRUE | ✕ No |
| parent gt mechanistically inconsistent ar | Parental results are compatible with autosomal recessive inheritance | FALSE | ✓ Yes |
| parent gt mechanistically inconsistent ar | Parental genetic data are missing, so inheritance cannot be checked | NA | ✕ No |
| compound het phase inconsistent | The two variants are arranged in a way that cannot explain disease together | TRUE | ✕ No |
| compound het phase inconsistent | The two variants are arranged in a way that could explain disease together | FALSE | ✓ Yes |
| compound het phase inconsistent | Information on how the variants are arranged is unavailable | NA | ✕ No |
| denovo mechanism not excluded | Family data rule out the variant being a new genetic change | TRUE | ✕ No |
| denovo mechanism not excluded | Family data allow the variant to be a new genetic change | FALSE | ✓ Yes |
| denovo mechanism not excluded | Parental genetic data are missing, so this cannot be assessed | NA | ✕ No |
| unaffected relative homozygous alt | An unaffected family member carries the same genetic change | TRUE | ✕ No |
| unaffected relative homozygous alt | No unaffected family member is known to carry the same change | FALSE | ✓ Yes |
| unaffected relative homozygous alt | Family health or genetic information is insufficient to assess this | NA | ✕ No |