{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/6b44a96e-4725-4e0f-adb2-46375b66f326/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1571601249", "label": "ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for IL2RG Version 2.1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010315", "id": "MONDO:0010315", "label": "T-B+ severe combined immunodeficiency due to gamma chain deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/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": "2026/4/24", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA413496508/MONDO:0010315/129/ci/CA413496508/MONDO:0010315/129.002", "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 is absent from gnomAD v4.1.0. (PM2_Supporting)", "contributionDate": { "date": "2026/4/24", "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": "CA413496508/MONDO:0010315/129/ci/CA413496508/MONDO:0010315/129.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/el/0/1606", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/ei/1/1607", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2026/4/24", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA413496508/MONDO:0010315/129/ci/CA413496508/MONDO:0010315/129.002", "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 reported in 2 patients meeting the PP4 phenotypic criteria (PMIDs 31031743, 36177038). Excluding the proband used to satisfy the PP4 criteria (PMID 36177038), the other patient is counted for PS4. PS4_Supporting is met. ", "contributionDate": { "date": "2026/4/24", "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": "CA413496508/MONDO:0010315/129/ci/CA413496508/MONDO:0010315/129.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/0/1606/1608", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/1/1607", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/0/1606", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/ei/1/1739", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2026/4/24", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA413496508/MONDO:0010315/129/ci/CA413496508/MONDO:0010315/129.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "One individual with this variant was diagnosed with X-SCID (0.5pt) (PMID 36177038). The patient showed a T-B+NK- lymphocyte profile (0.5pt + 1pt), and an absence of STAT5 phosphorylation upon IL-2 stimulation (other possible variants were not excluded) (1.5pt). The lymphopenia was resolved by IL2RG gene therapy (CNV testing not reported, 4.5pt). 8pt in total, PP4_Strong is met.", "contributionDate": { "date": "2026/4/24", "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": "CA413496508/MONDO:0010315/129/ci/CA413496508/MONDO:0010315/129.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2026/4/24", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA413496508/MONDO:0010315/129/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA413496508/MONDO:0010315/129/ci/CA413496508/MONDO:0010315/129.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "comments": "Another missense variant c.455T>C (p.Val152Ala), ClinVar Variation ID 36386, in the same codon has been classified as pathogenic for SCID by the ClinGen SCID VCEP. PM5 is met.", "contributionDate": { "date": "2026/4/24", "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": "CA413496508/MONDO:0010315/129/ci/CA413496508/MONDO:0010315/129.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA413496508/MONDO:0010315/129", "metadata": { "created": "2026-04-24T02:02:42.197Z", "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, 24 Apr 2026 02:02:42 -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": "6b44a96e-4725-4e0f-adb2-46375b66f326", "variant": { "@id": "https://reg.genome.network/allele/CA413496508", "id": "CAR:CA413496508", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000206.3:c.455T>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000206.3(IL2RG):c.455T>G (p.Val152Gly)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T01:58:10.385Z" } }, "status": { "code": 200, "name": "OK" } }