Clinical-Genomics / scout

VCF visualization interface
https://clinical-genomics.github.io/scout
BSD 3-Clause "New" or "Revised" License
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ACMG benign modifiers apply to is_likely_pathogenic and is_pathogenic #4645

Closed ViktorHy closed 1 month ago

ViktorHy commented 1 month ago

We noticed when filling out the ACMG classifier that modifiers to benign classes would apply to the pathogenic terms as well.

We had this situation: PS3_moderate PP1_moderate PP3

This correctly defaults to uncertain significance. But, when adding a benign BS1_supporting

The classification instead turned into likely_pathogenic

It seems like this code snippet does not separate whether or not a term is of pathogenic origin or benign https://github.com/Clinical-Genomics/scout/blob/d448461287114e5a79d684ed2e67c913aea1906e/scout/utils/acmg.py#L193

You can test this further by just adding benign classifications and giving them strong modifiers. This results in pathogenic and likely_pathogenic outcomes. As I understand it, it's quite rare to have modifiers on benign classes but in this case, following the strict guidelines the geneticist came to this outcome.