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acmg docs refactoring
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@gromdimon
gromdimon committed Sep 25, 2023
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2 changes: 1 addition & 1 deletion .gitignore
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Expand Up @@ -203,7 +203,7 @@ tags

### VisualStudioCode ###
.vscode/*
!.vscode/settings.json
.vscode/settings.json
!.vscode/tasks.json
!.vscode/launch.json
!.vscode/extensions.json
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66 changes: 36 additions & 30 deletions frontend/src/api/acmgSeqVar.ts
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Expand Up @@ -106,126 +106,132 @@ const ACMG_CRITERIA_DEFS: Map<AcmgCriteria, CriteriaDefinition> = new Map(
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicVeryStrong,
label: 'PVS1',
hint: 'Very strong evidence of pathogenicity',
description:
'Null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where LOF is a known mechanism of disease'
description: `Null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon,
single or multi-exon deletion) in a gene where LOF is a known mechanism of disease. Caution!
PVS1 confronts with PM4 and PP3! Use as strong if not subject to NMD but >10% of the protein
are affected.`
},
{
criteria: AcmgCriteria.Ps1,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicStrong,
label: 'PS1',
hint: 'same amino acid change',
description:
'Same amino acid change as a previously established pathogenic variant regardless of nucleotide change'
description: `Same amino acid change as a previously established pathogenic variant regardless of
nucleotide change. CAVE not applicable for same nucleotide change, for same nucleotide
change use PS4.`
},
{
criteria: AcmgCriteria.Ps2,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicStrong,
label: 'PS2',
hint: 'de novo (both maternity and paternity confirmed)',
description:
'De novo (both maternity and paternity confirmed) in a patient with the disease and no family history'
description: `De novo (both maternity and paternity confirmed) in a patient with the disease and no
family history.`
},
{
criteria: AcmgCriteria.Ps3,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicStrong,
label: 'PS3',
hint: 'well-established in vitro or in vivo functional studies',
description:
'Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product'
description: `Well-established in vitro or in vivo functional studies supportive of a damaging effect on
the gene or gene product.`
},
{
criteria: AcmgCriteria.Ps4,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicStrong,
label: 'PS4',
hint: 'prevalence in disease controls',
description:
'The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls'
description: `The prevalence of the variant in affected individuals is significantly increased compared
with the prevalence in controls.`
},
{
criteria: AcmgCriteria.Pm1,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicModerate,
label: 'PM1',
hint: 'variant in hotspot (missense)',
description:
'Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation'
description: `Located in a mutational hot spot and/or critical and well-established functional domain
(e.g., active site of an enzyme) without benign variation.`
},
{
criteria: AcmgCriteria.Pm2,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicModerate,
label: 'PM2',
hint: 'absent from controls (or at extremely low frequency if recessive)',
description:
'Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium'
description: `Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing
Project, 1000 Genomes Project, or Exome Aggregation Consortium. New recommendation: use on
supporting only.`
},
{
criteria: AcmgCriteria.Pm3,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicModerate,
label: 'PM3',
hint: 'AR: trans with known pathogenic',
description: 'For recessive disorders, detected in trans with a pathogenic variant'
description: `For recessive disorders, detected in trans with a pathogenic variant.`
},
{
criteria: AcmgCriteria.Pm4,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicModerate,
label: 'PM4',
hint: 'protein length change',
description:
'Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants'
description: `Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region
or stop-loss variants. Do not use in combination with PVS1 or PP3.`
},
{
criteria: AcmgCriteria.Pm5,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicModerate,
label: 'PM5',
hint: 'literature: AA exchange same pos',
description:
'Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before'
description: `Novel missense change at an amino acid residue where a different missense change determined
to be pathogenic has been seen before.`
},
{
criteria: AcmgCriteria.Pm6,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicModerate,
label: 'PM6',
hint: 'assumed de novo',
description: 'Assumed de novo, but without confirmation of paternity and maternity'
description: `Assumed de novo, but without confirmation of paternity and maternity.`
},
{
criteria: AcmgCriteria.Pp1,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicSupporting,
label: 'PP1',
hint: 'cosegregates in family',
description:
'Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease'
description: `Cosegregation with disease in multiple affected family members in a gene definitively known
to cause the disease.`
},
{
criteria: AcmgCriteria.Pp2,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicSupporting,
label: 'PP2',
hint: 'few missense in gene',
description:
'Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease'
description: `Missense variant in a gene that has a low rate of benign missense variation and in which
missense variants are a common mechanism of disease.`
},
{
criteria: AcmgCriteria.Pp3,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicSupporting,
label: 'PP3',
hint: 'predicted pathogenic',
description:
'Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)'
description: `Multiple lines of computational evidence support a deleterious effect on the gene or gene
product (conservation, evolutionary, splicing impact, etc.). Do not use in combination with
PVS1 or PM4.`
},
{
criteria: AcmgCriteria.Pp4,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicSupporting,
label: 'PP4',
hint: 'phenotype/pedigree match gene',
description:
"Patient's phenotype or family history is highly specific for a disease with a single genetic etiology"
description: `Patient's phenotype or family history is highly specific for a disease with a single
genetic etiology.`
},
{
criteria: AcmgCriteria.Pp5,
defaultEvidenceLevel: AcmgEvidenceLevel.PathogenicSupporting,
label: 'PP5',
hint: 'reliable source: pathogenic',
description:
'Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratoryto perform an independent evaluation'
description: `Reputable source recently reports variant as pathogenic, but the evidence is not available
to the laboratoryto perform an independent evaluation. Note: Not recommended to use anymore,
use PS3 and PS4 at different levels of evidence.`
},
{
criteria: AcmgCriteria.Ba1,
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8 changes: 3 additions & 5 deletions frontend/src/components/VariantDetails/AcmgRating.vue
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Expand Up @@ -111,6 +111,7 @@ onMounted(async () => {

<template>
<v-row>
<v-col cols="12" md="3"></v-col>
<v-col cols="12" md="6" class="section">
<div>
<div>
Expand Down Expand Up @@ -145,6 +146,7 @@ onMounted(async () => {
</div>
</div>
</v-col>
<v-col cols="12" md="3"></v-col>
</v-row>
<v-row style="margin-bottom: 15px">
<v-col>
Expand Down Expand Up @@ -215,14 +217,10 @@ onMounted(async () => {
</v-col>
</v-row>
<v-row>
<v-col>
<v-col class="d-flex flex-row flex-wrap">
<v-btn color="black" variant="outlined" @click="showFailed = !showFailed">
{{ showFailed ? 'Hide' : 'Show' }} failed criteria
</v-btn>
</v-col>
</v-row>
<v-row>
<v-col class="d-flex flex-row flex-wrap">
<v-table>
<thead>
<tr>
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19 changes: 13 additions & 6 deletions frontend/src/views/ACMGCriteriaDocs.vue
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Expand Up @@ -18,15 +18,17 @@ import HeaderDefault from '@/components/HeaderDefault.vue'
<p>
Description: Null variant (nonsense, frameshift, canonical ±1 or 2 splice sites,
initiation codon, single or multi-exon deletion) in a gene where LOF is a known
mechanism of disease
mechanism of disease. Caution! PVS1 confronts with PM4 and PP3! Use as strong if not
subject to NMD but >10% of the protein are affected.
</p>
<p>Hint: Null variant</p>
</li>
<li>
<h3>PS1 - Same amino acid change</h3>
<p>
Description: Same amino acid change as a previously established pathogenic variant
regardless of nucleotide change
regardless of nucleotide change. CAVE not applicable for same nucleotide change, for
same nucleotide change use PS4.
</p>
<p>Hint: Literature: this AA exchange</p>
</li>
Expand Down Expand Up @@ -66,7 +68,8 @@ import HeaderDefault from '@/components/HeaderDefault.vue'
<h3>PM2 - Absent from controls</h3>
<p>
Description: Absent from controls (or at extremely low frequency if recessive) in
Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. New
recommendation: use on supporting level only.
</p>
<p>Hint: Rare; &lt; 1:20,000 in ExAC</p>
</li>
Expand All @@ -81,7 +84,8 @@ import HeaderDefault from '@/components/HeaderDefault.vue'
<h3>PM4 - Protein length changes</h3>
<p>
Description: Protein length changes as a result of in-frame deletions/insertions in
a nonrepeat region or stop-loss variants
a nonrepeat region or stop-loss variants. Do not use in combination with PVS1 or
PP3.
</p>
<p>Hint: Protein length change</p>
</li>
Expand Down Expand Up @@ -120,7 +124,8 @@ import HeaderDefault from '@/components/HeaderDefault.vue'
<h3>PP3 - Multiple lines of computational evidence</h3>
<p>
Description: Multiple lines of computational evidence support a deleterious effect
on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
on the gene or gene product (conservation, evolutionary, splicing impact, etc.). Do
not use in combination with PVS1 or PM4.
</p>
<p>Hint: Predicted pathogenic >= 2</p>
</li>
Expand All @@ -136,7 +141,9 @@ import HeaderDefault from '@/components/HeaderDefault.vue'
<h3>PP5 - Reputable source reports variant as pathogenic</h3>
<p>
Description: Reputable source recently reports variant as pathogenic, but the
evidence is not available to the laboratory to perform an independent evaluation
evidence is not available to the laboratory to perform an independent evaluation.
Note: Not recommended to use anymore, use PS3 and PS4 at different levels of
evidence.
</p>
<p>Hint: Reliable source: pathogenic</p>
</li>
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