ACMGv4 Human Observation — Case Data Model (Working Notes)¶

Working Draft

These are working notes for extracting and documenting the JSON case structures used in the ACMGv4 Human Observation evidence framework. This file is a companion to ACMGv4-Case-DM-Schema.md, which derives the superset schema and attribute matrix from the examples below.

General Case Attributes¶

Every case carries these attributes, which determine routing into the appropriate CLN group.

{
  "case_id": "...",
  "moi": "...",
  "zygosity": "...",
  "mde_affected": "T|F|U",
  "well_phenotyped": "T|F|U"
}

CLN_UAF — Unaffected Observations¶

Cases where the individual has the VBC but is not affected with the MDE.

UAF Monoallelic (AD/XLD)¶

UAF_AD/XLD_Agg_Per_Case_Type.98

{
  "case_id": "99098-W",
  "age_matched_penetrance": "NEAR-100"  // NEAR-100 | 80-100 | BELOW-80
}

UAF Biallelic (AR/XLR)¶

UAF_AR/XLR_Agg_Per_Case_Type.99

{
  "case_id": "3832.Z99",
  "age_matched_penetrance": "NEAR-100",  // NEAR-100 | 80-100 | BELOW-80
  "zygosity_plus_type": "TRANS-CONF-PATH"  // TRANS-CONF-PATH | TRANS-CONF-LIKPATH | HOM-HEMI
}

CLN_ALT — Affected Observations with Alternate Cause¶

Cases where the individual is affected, but an alternate genetic cause explains the disease.

ALT_Var — Additional P/LP Variant in Same Gene¶

ALT_VAR_AXLD.1.AggCaseTyp.20

{
  "case_id": "1005.Z",
  "additional_var": {
    "id": "(optional — hgvs, caid, clinvar, etc.)",
    "classification": "PLP",  // PLP | VUS | BLB
    "gene": {
      "same_as_VBC": true,
      "associated_with_MDE": true
    }
  },
  "severity_comparison": "GREATER-THAN-AD"  // GREATER-THAN-AD | SAME-AS-AD
}

ALT_Gene — Additional P/LP Variant in Different Gene¶

ALT_GENE_AXLD.1.AggCaseTyp.30

{
  "case_id": "3512-XYZ",
  "additional_var": {
    "id": "(optional — hgvs, caid, clinvar, etc.)",
    "classification": "PLP",  // PLP | VUS | BLB
    "gene": {
      "same_as_VBC": false,
      "associated_with_MDE": true
    }
  },
  "severity_comparison": "SAME-AS-AD"  // GREATER-THAN-AD | SAME-AS-AD
}

CLN_AFF — Affected Observations (Standard)¶

Standard affected cases — not de novo and not alternate cause.

AFF Monoallelic (AD/XLD)¶

AFF_AXLD.1.AggCaseTyp.1 — Specific phenotype, all genes tested, no VUS

{
  "case_id": "001.A",
  "pheno_spec_gene_type": "SPECIFIC",
  "all_rel_disorder_genes_tested": true,
  "vois_exist": false
}

AFF_AXLD.1.AggCaseTyp.2 — Consistent phenotype, not all genes tested, VUS present

{
  "case_id": "001.X2",
  "pheno_spec_gene_type": "CONSISTENT",
  "all_rel_disorder_genes_tested": false,
  "vois_exist": true
}

AFF_AXLD.1.AggCaseTyp.3 — Inconsistent phenotype

{
  "case_id": "001.Y",
  "pheno_spec_gene_type": "INCONSISTENT"
}

AFF Biallelic (AR/XLR/SD)¶

AFF_AXLR.1.AggCaseTyp.4 — Consistent phenotype, VUS present, trans-confirmed

{
  "case_id": "099.N12",
  "pheno_spec_gene_type": "CONSISTENT",
  "all_rel_disorder_genes_tested": false,
  "vois_exist": true,
  "zygosity_plus_type": "TRANS-CONF-VUS"
}

AFF_AXLR.1.AggCaseTyp.5 — Specific phenotype, all genes tested, homozygous/hemizygous

{
  "case_id": "409.F1",
  "pheno_spec_gene_type": "SPECIFIC",
  "all_rel_disorder_genes_tested": true,
  "vois_exist": false,
  "zygosity_plus_type": "HOM-HEMI"
}

CLN_DNV — Affected with De Novo Variant¶

De novo variant occurrence. MOI must be AD, SD, XLD, or XLR only.

CLN_DNV.1.AggCaseTyp.10 — Confirmed parental testing

{
  "case_id": "001.B",
  "pheno_spec_gene_type": "SPECIFIC",
  "all_rel_disorder_genes_tested": true,
  "confirmed_parental": true
}

CLN_DNV.1.AggCaseTyp.11 — Without confirmed parental testing

{
  "case_id": "888.A",
  "pheno_spec_gene_type": "SPECIFIC",
  "all_rel_disorder_genes_tested": true,
  "confirmed_parental": false
}