{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/7228b2b2-4c3d-4184-ab25-641179a4ed7d/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1564418400", "label": "ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ADA Version 2.2", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.2" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0007064", "id": "MONDO:0007064", "label": "adenosine deaminase deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2026/10/30", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0018", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0018", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA266020/MONDO:0007064/114/ci/CA266020/MONDO:0007064/114.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "Red blood cells from at least one patient with this variant who was diagnosed with SCID showed an elevated %dAXP of 46% along with absent ADA activity, which is highly specific for ADA-SCID (5 pts; unpublished data, M. Hershfield). Total: 5.0 points, meeting PP4_Moderate.", "contributionDate": { "date": "2026/10/30", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA266020/MONDO:0007064/114/ci/CA266020/MONDO:0007064/114.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2026/10/30", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA266020/MONDO:0007064/114/ci/CA266020/MONDO:0007064/114.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "Grpmax filtering allele frequency of this variant is 0.0000088 ([ancestry group]) in gnomAD v4.1.1, which is lower than the ClinGen SCID VCEP threshold (<0.0001742) for PM2_Supporting for ADA, therefore meets this criterion (PM2_Supporting). No homozygotes have been observed.\n", "contributionDate": { "date": "2026/10/30", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA266020/MONDO:0007064/114/ci/CA266020/MONDO:0007064/114.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/ei/1/1826", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2026/10/30", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0039", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0039", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/el/0/1825/1827", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA266020/MONDO:0007064/114/ci/CA266020/MONDO:0007064/114.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "In unpublished data from M. Hershfield, expression of p.Gly20Arg in the ADA-deleted E. coli strain SØ3834 yielded <0.05% of wild-type ADA activity, consistent with Group I per the Arredondo-Vega classification (PMID: 9758612). This meets PS3_Moderate.", "contributionDate": { "date": "2026/10/30", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA266020/MONDO:0007064/114/ci/CA266020/MONDO:0007064/114.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/0/1825/1827", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/1/1826", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/0/1825", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2026/10/30", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0058", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0058", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA266020/MONDO:0007064/114/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA266020/MONDO:0007064/114/ci/CA266020/MONDO:0007064/114.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "This variant has been detected in at least four individuals with ADA-SCID. Patient SC44 was homozygous for c.58G>A, with consanguinity reported (0.5 pt; PMID 32445296). Patient WG548 was homozygous for c.58G>A and was from a small isolated inbred community with a history of consanguinity (0.5 pt; PMID 8299233). One Egyptian patient with a T-B-NK- phenotype was homozygous for c.58G>A; consanguinity was not reported for this individual (0.5 pt; PMID 35482138). One patient was compound heterozygous for c.58G>A and c.956_960del (p.Glu319GlyfsTer3), classified Pathogenic by the SCID-VCEP, with phase unknown (0.5 pt; PMID 41011036; possibly the same individual as Patient 39 in PMID 38355973, counted once). Total: 2.0 points, meeting PM3_Strong.", "contributionDate": { "date": "2026/10/30", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA266020/MONDO:0007064/114/ci/CA266020/MONDO:0007064/114.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114/0/1651", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA266020/MONDO:0007064/114", "metadata": { "created": "2026-10-30T03:06:39.157Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Fri, 30 Oct 2026 03:06:39 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "7228b2b2-4c3d-4184-ab25-641179a4ed7d", "variant": { "@id": "https://reg.genome.network/allele/CA266020", "id": "CAR:CA266020", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000022.4:c.58G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000022.4(ADA):c.58G>A (p.Gly20Arg)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-04T11:48:12.775Z" } }, "status": { "code": 200, "name": "OK" } }