Reimplement AutoPS1PM5

[gromdimon]

Is your feature request related to a problem? Please describe.
We have AutoPS1PM5 after the implementation of #68 . We need to update he implementation

Describe the solution you'd like

• Reimplement
• Test unit
• Test integration
• Update docs

Describe alternatives you've considered
N/A

Additional context
Info for PSW1 and PM5
PS1 (same amino acid)

Original Definition

Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.

Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.

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

Preconditions / Precomputations

• If the variant is not a missense variant then this criterion is skipped.

Implemented Criterion

• Consider all equivalent missense variants in ClinVar.
• If at least one of the variant then this criterion is triggered.
  • If the variant has zero stars in ClinVar then we report PS1_Supporting only
  • If the variant has only one star in ClinVar then we report PS1_Moderate only
  • If the variant has two stars in ClinVar then we report PS1
  • If the variant has three stars or above in ClinVar then we report PS1_VeryStrong

User Report

• The selected variant in ClinVar and with assessment its star status with accession.
• All alternate variants in Clinvar with assessments and star status with accessions.

Literature

N/A

Caveats

• The wording of "established pathogenic" variant is not clear so we use the steps from above.
• Note that this also depends on disease match which the user must confirm manually.

PM5

PM5 (overlapping missense)

Original Definition

Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.

Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.

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

Preconditions / Precomputations

• If the variant is on a nuclear chromosome
  • If it is not a missense variant then this criterion is skipped.
• If the variant is on chrMT and not missense and not on a tRNA gene then this criterion is skipped.

Implemented Criterion

• If the variant is on a nuclear chromosome:
  • If the variant is at the same position as a pathogenic missense variant then this criterion is triggered.
• If the variant is on chrMT:
  • If the variant is a missense variant and at the same position as a pathogenic one then the criterion is triggered.
  • If the variant is on a tRNA gene and at the same position as a pathogenic one then the criterion is triggered as PM5_Supporting.

User Report

• The overlapping variant used for criterion.
• Any alternative overlapping variants not chosen.

Literature

• Richards et al. (2018) describes the criterion for nuclear chromosomes.
• McCormick et al. (2020) describes the criterion for chrMT.

Caveats

N/A

InterVar paragraph

PS1 and PM5 by Automated Scoring
Generally speaking, if one missense variant is pathogenic, then a different nucleotide change that results in the same amino acid alteration should also be pathogenic for PS1. However, if a different nucleotide change results in a different amino acid change, then it suggests moderate evidence of pathogenicity by PM5. We first filtered ClinVar (subject to the same data-cleaning procedure described above), picked out all missense variants annotated as pathogenic, and stored the amino acid changes in an InterVar-specific database. We also inferred the splicing impact of these exonic missense variants by ANNOVAR from the “dbscsnv11” database to assess the possibility that they act through splicing disruption rather than amino acid changes. If a variant supplied by the user results in the same amino acid change, the PS1 value will be assigned as 1. However, if a variant supplied by the user results in a different amino acid change, then PM5 will be assigned as 1.