Is your feature request related to a problem? Please describe.
Aftre implementation of #76 we need to properly finish necessary methods in AutoPP2BP1 and test it.
Describe the solution you'd like
Implement _get_missense_variants method
Test it (unit + e2e)
Rewrite docstrings
Describe alternatives you've considered
N/A
Additional context
Some info for PP2 and BP1
PP2 (missense)
Original Definition
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
-- Richards et al. (2015); Table 4
Preconditions / Precomputations
If the variant is on chrMT then this criterion is skipped according to McCormick et al. (2020).
If the variant is not a missense variant then this criterion is skipped.
Implemented Criterion
If the ratio of pathogenic missense variants over all non-VUS missense variants is greater than 0.808 then this criterion is triggered.
User Report
Report the ratio of pathogenic missense variants over all non-VUS missense variants.
Literature
McCormick et al. (2020) describe the ACMG criteria for chrMT variants.
Caveats
We currently use the threshold from PMID:30376034 <https://pubmed.ncbi.nlm.nih.gov/30376034/>__ and are lacking our own calibration.
Notes
This criterion is similar to :ref:acmg_seqvars_criteria-bp1
BP1
BP1 (missense)
Original Definition
Missense variant in a gene for which primarily truncating variants are known to cause disease
-- Richards et al. (2015); Table 4
Preconditions / Precomputations
If the criterion BA1 triggered then this criterion is skipped.
If the variant is on chrMT then this criterion is skipped according to McCormick et al. (2020).
If the variant is not a missense variant then this criterion is skipped.
Implemented Criterion
If the ratio of benign missense variants over all non-VUS missense variants is greater than 0.569 then this criterion is triggered.
User Report
Report the ratio of benign missense variants over all non-VUS missense variants together with threshold.
Literature
McCormick et al. (2020) describe the ACMG criteria for chrMT variants.
Caveats
We currently use the threshold from PMID:30376034 <https://pubmed.ncbi.nlm.nih.gov/30376034/>__ and are lacking our own calibration.
Notes
Intervar
PP2 and BP1 by Automated Scoring
For many genes, the spectrum or distribution of pathogenic and benign variants can be informative for the pathogenicity status. For a given gene, if the missense variants are common causes of the disorder and the gene also has very few benign variants, then a missense variant in this gene can be supporting evidence for pathogenicity, and PP2 will be applied. However, if the truncating variants are major causes of the disease, then a missense variant in this gene can be supporting evidence for a benign status, and BP1 will be applied.
We annotated all variants in ClinVar (subject to the same data-cleaning procedure described above). For a given gene, if most of the pathogenic variants (>80% and at least one variant) are missense, and if a small proportion (<10% and less than one variant) of missense variants are benign, then for missense variants, PP2 will be assigned as 1. The treatment for BP1 is similar to that for PP2, but we assess whether most of pathogenic variants (>80% and at least one variant) are truncating variants. The truncating variants are defined as stop-gain, stop-loss, frameshift indel, or those disrupting splice sites. If the user’s variants are missense in this gene, BP1 will be assigned as 1.
Is your feature request related to a problem? Please describe. Aftre implementation of #76 we need to properly finish necessary methods in AutoPP2BP1 and test it.
Describe the solution you'd like
_get_missense_variantsmethodDescribe alternatives you've considered N/A
Additional context Some info for PP2 and BP1
PP2 (missense)
Original Definition
Preconditions / Precomputations
Implemented Criterion
User Report
Literature
Caveats
PMID:30376034 <https://pubmed.ncbi.nlm.nih.gov/30376034/>__ and are lacking our own calibration.Notes
acmg_seqvars_criteria-bp1BP1
BP1 (missense)
Original Definition
Preconditions / Precomputations
Implemented Criterion
User Report
Literature
Caveats
PMID:30376034 <https://pubmed.ncbi.nlm.nih.gov/30376034/>__ and are lacking our own calibration.Notes
Intervar
PP2 and BP1 by Automated Scoring For many genes, the spectrum or distribution of pathogenic and benign variants can be informative for the pathogenicity status. For a given gene, if the missense variants are common causes of the disorder and the gene also has very few benign variants, then a missense variant in this gene can be supporting evidence for pathogenicity, and PP2 will be applied. However, if the truncating variants are major causes of the disease, then a missense variant in this gene can be supporting evidence for a benign status, and BP1 will be applied. We annotated all variants in ClinVar (subject to the same data-cleaning procedure described above). For a given gene, if most of the pathogenic variants (>80% and at least one variant) are missense, and if a small proportion (<10% and less than one variant) of missense variants are benign, then for missense variants, PP2 will be assigned as 1. The treatment for BP1 is similar to that for PP2, but we assess whether most of pathogenic variants (>80% and at least one variant) are truncating variants. The truncating variants are defined as stop-gain, stop-loss, frameshift indel, or those disrupting splice sites. If the user’s variants are missense in this gene, BP1 will be assigned as 1.