search

bihealth / auto-acmg

Automatic classification of sequence variants and CNVs according to ACMG criteria.
GNU General Public License v3.0
6 stars 0 forks source link

Implement `PM3` and `BP2` criteria #73

Closed gromdimon closed 1 month ago

gromdimon commented 5 months ago

Is your feature request related to a problem? Please describe. Implement PM3 and BP2 criteria. However, no automatation exists, so it can be tricky.

Describe the solution you'd like

Describe alternatives you've considered N/A

Additional context

PM3

PM3 (recessive in trans)

No automation has been implemented.

Original Definition

For recessive disorders, detected in trans with a pathogenic variant.

Note: This requires testing of parents (or offspring) to determine phase.

-- Richards et al. (2015); Table 4

BP2

BP2 (recessive in trans)

No automation has been implemented.

Original Definition

Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder; or observed in cis with a pathogenic variant in any inheritance pattern

-- Richards et al. (2015); Table 4

Intervar

PM3 and BP2 by Manual Scoring The pathogenicity of a variant also needs to be evaluated on the basis of whether variants with known pathogenicity exist in cis or trans with it. InterVar does not know the cis/trans status for variants, so this needs to be provided by users in the second step (manual adjustment) of InterVar. For two heterozygous variants that are present in a gene associated with recessive disorders, if one is pathogenic and the other is located in trans, then moderate evidence of PM3 will be applied. If more than two variants are observed in trans, then moderate evidence for pathogenicity can be upgraded to strong. If the variants are present in a gene associated with dominant diseases, yet one variant is pathogenic and the other is located in trans, then supporting evidence of benign status will be applied to BP2 for the other variant. Regardless of models of disease inheritance, for two variants, if one is pathogenic and the other is observed in cis, then BP2 will be applied for the other variant.

gromdimon commented 1 month ago

Due to data restrictions, this criteria cannot be implemented for now. -> Archiving