diff --git a/frontend/src/components/VariantDetails/AcmgRating.vue b/frontend/src/components/VariantDetails/AcmgRating.vue index 41bb4443..502fb58e 100644 --- a/frontend/src/components/VariantDetails/AcmgRating.vue +++ b/frontend/src/components/VariantDetails/AcmgRating.vue @@ -14,7 +14,7 @@ const props = defineProps({ const acmgRatingStore = useVariantAcmgRatingStore() const variantInfoStore = useVariantInfoStore() -const emptyAcmgRatingTemplate = { +const emptyAcmgRatingTemplate: any = { pvs1: 0, ps1: 0, ps2: 0, @@ -210,9 +210,7 @@ const convertEmptyToNull = (classOverride: any) => { } const onSubmitAcmgRating = async () => { - const acmgRatingToSubmitNoAuto = copy(acmgRatingToSubmit.value) - delete acmgRatingToSubmitNoAuto['class_auto'] - const acmgRatingToSubmitEmpty = isEqual(acmgRatingToSubmitNoAuto, emptyAcmgRatingTemplate) + const acmgRatingToSubmitEmpty = isEqual(acmgRatingToSubmit, emptyAcmgRatingTemplate) if (acmgRatingStore.acmgRating && acmgRatingToSubmitEmpty) { // IS not empty but SHOULD be empty, so delete the ACMG rating await acmgRatingStore.deleteAcmgRating() @@ -244,6 +242,239 @@ onMounted(async () => { resetAcmgRating() } }) + +const acmgCriteriaInfo = { + pathogenic: { + 'very-strong-evidence': { + name: 'Very Strong Evidence', + criteria: [ + { + name: 'PVS1', + id: 'pvs1', + 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', + hint: 'null variant' + } + ] + }, + 'strong-evidence': { + name: 'Strong Evidence', + criteria: [ + { + name: 'PS1', + id: 'ps1', + description: + 'Same amino acid change as a previously established pathogenic variant regardless of nucleotide change', + hint: 'literature: this AA exchange' + }, + { + name: 'PS2', + id: 'ps2', + description: + 'De novo (both maternity and paternity confirmed) in a patient with the disease and no family history', + hint: 'confirmed de novo' + }, + { + name: 'PS3', + id: 'ps3', + description: + 'Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product', + hint: 'supported by functional studies' + }, + { + name: 'PS4', + id: 'ps4', + description: + 'The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls', + hint: 'prevalende in disease controls' + } + ] + }, + 'moderate-evidence': { + name: 'Moderate Evidence', + criteria: [ + { + name: 'PM1', + id: 'pm1', + 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', + hint: 'variant in horspot (missense)' + }, + { + name: 'PM2', + id: 'pm2', + description: + 'Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium', + hint: 'rare in 1:20.000 in ExAC' + }, + { + name: 'PM3', + id: 'pm3', + description: 'For recessive disorders, detected in trans with a pathogenic variant', + hint: 'AR: trans with known pathogenic' + }, + { + name: 'PM4', + id: 'pm4', + description: + 'Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants', + hint: 'protein length change' + }, + { + name: 'PM5', + id: 'pm5', + description: + 'Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before', + hint: 'literature: AA exchange same pos' + }, + { + name: 'PM6', + id: 'pm6', + description: 'Assumed de novo, but without confirmation of paternity and maternity', + hint: 'assumed de novo' + } + ] + }, + 'supporting-evidence': { + name: 'Supporting Evidence', + criteria: [ + { + name: 'PP1', + id: 'pp1', + description: + 'Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease', + hint: 'cosegregates in family' + }, + { + name: 'PP2', + id: 'pp2', + 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', + hint: 'few missense in gene' + }, + { + name: 'PP3', + id: 'pp3', + description: + 'Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)', + hint: 'predicted pathogenic' + }, + { + name: 'PP4', + id: 'pp4', + description: + "Patient's phenotype or family history is highly specific for a disease with a single genetic etiology", + hint: 'phenotype/pedigree match gene' + }, + { + name: 'PP5', + id: 'pp5', + description: + 'Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratoryto perform an independent evaluation', + hint: 'reliable source: pathogenic' + } + ] + } + }, + benign: { + 'standalone-evidence': { + name: 'Standalone Evidence', + criteria: [ + { + name: 'BA1', + id: 'ba1', + description: + 'Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium', + hint: 'allele frequency > 5%' + } + ] + }, + 'strong-evidence': { + name: 'Strong Evidence', + criteria: [ + { + name: 'BS1', + id: 'bs1', + description: 'Allele frequency is greater than expected for disorder', + hint: 'disease: allele freq. too high' + }, + { + name: 'BS2', + id: 'bs2', + description: + 'Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age', + hint: 'observed in healthy individual' + }, + { + name: 'BS3', + id: 'bs3', + description: + 'Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing', + hint: 'functional studies: benign' + }, + { + name: 'BS4', + id: 'bs4', + description: 'Lack of segregation in affected members of a family', + hint: 'lack of segregation' + } + ] + }, + 'supporting evidence': { + name: 'Supporting Evidence', + criteria: [ + { + name: 'BP1', + id: 'bp1', + description: + 'Missense variant in a gene for which primarily truncating variants are known to cause disease', + hint: 'missense in gene with truncating' + }, + { + name: 'BP2', + id: 'bp2', + description: + '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', + hint: 'other variant is causative' + }, + { + name: 'BP3', + id: 'bp3', + description: + 'In-frame deletions/insertions in a repetitive region without a known function', + hint: 'in-frame del/ins in repeat' + }, + { + name: 'BP4', + id: 'bp4', + description: + 'Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary,splicing impact, etc.)', + hint: 'predicted benign' + }, + { + name: 'BP5', + id: 'bp5', + description: 'Variant found in a case with an alternate molecular basis for disease', + hint: 'other variant is causative' + }, + { + name: 'BP6', + id: 'bp6', + description: + 'Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation', + hint: 'reliable source: benign' + }, + { + name: 'BP7', + id: 'bp7', + description: + 'A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved', + hint: 'synonymous: no splice effect' + } + ] + } + } +}