{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/0136b3ad-65d9-44c7-ae99-4d4d38a96521/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 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "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/CA409118697/MONDO:0007064/114/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA409118697/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": "2024/2/21", "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/CA409118697/MONDO:0007064/114/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA409118697/MONDO:0007064/114/ci/CA409118697/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": "The filtering allele frequency (the upper threshold of the 95% CI of 2/1111992 alleles) of the c.975+1G>A variant in ADA is 0.0000003 for European (non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.0001742) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). No homozygotes have been observed in gnomAD.", "contributionDate": { "date": "2024/2/21", "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": "CA409118697/MONDO:0007064/114/ci/CA409118697/MONDO:0007064/114.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA409118697/MONDO:0007064/114/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA409118697/MONDO:0007064/114/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316", "id": "CG-PCER-AGENT:CG_50091_EP170474596929316", "type": "Agent" }, "contributionDate": { "date": "2024/2/21", "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/0017", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000220", "id": "SEPIO:0000220", "label": "Pathogenic Very Strong" }, "id": "0017", "label": "PVS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA409118697/MONDO:0007064/114/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA409118697/MONDO:0007064/114/ci/CA409118697/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": "The c.975+1G>A (NM_000022.4) variant in ADA occurs within the canonical splice site donor of intron 10. It is expected to disrupt RNA splicing, disrupting the reading frame, and is predicted to undergo NMD. (PVS1). \n", "contributionDate": { "date": "2024/2/21", "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": "CA409118697/MONDO:0007064/114/ci/CA409118697/MONDO:0007064/114.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA409118697/MONDO:0007064/114/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA409118697/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": "2024/2/21", "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/CA409118697/MONDO:0007064/114/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA409118697/MONDO:0007064/114/ci/CA409118697/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": "At least one patient with this variant displayed * Increased dAdo nucleotides (dATP or dAXP) in pretreatment erythrocytes (2pts), which is highly specific for ADA SCID (PP4_Moderate, PMID: 8227344).", "contributionDate": { "date": "2024/2/21", "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": "CA409118697/MONDO:0007064/114/ci/CA409118697/MONDO:0007064/114.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA409118697/MONDO:0007064/114", "metadata": { "created": "2024-09-28T04:04:53.016Z", "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": "Sat, 28 Sep 2024 04:04:52 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "0136b3ad-65d9-44c7-ae99-4d4d38a96521", "variant": { "@id": "https://reg.genome.network/allele/CA409118697", "id": "CAR:CA409118697", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000022.4:c.975+1G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000022.4(ADA):c.975+1G>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T12:04:38.995Z" } }, "status": { "code": 200, "name": "OK" } }