{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b0b1fd47-57a4-4bc9-be3c-ffee5a993886/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1610842289", "label": "ClinGen Antibody Deficiencies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PIK3CD Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0014222", "id": "MONDO:0014222", "label": "immunodeficiency 14", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/el/0/1705", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/ei/1/1706", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA338300169/MONDO:0014222/141/el/0/1705/1707", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "This variant has been identified as a de novo occurrence with unconfirmed parental relationships in 1 individual with immunodeficiency 14. The individual met phenotypic criteria (>10 phenotypic points) and had alternative causes in other loci excluded by genotyping, which together are highly consistent with APDS (PS2_Moderate; PMID: 28428270).", "contributionDate": { "date": "2025/12/23", "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": "CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1705/1707", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/1/1706", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1705", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA338300169/MONDO:0014222/141/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300169/MONDO:0014222/141/ci/EV000001943", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "When overexpressed in healthy T cells, this variant resulted in increased phosphorus-AKT. ", "contributionDate": { "date": "2025/12/23", "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": "CA338300169/MONDO:0014222/141/ci/EV000001943", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/28414062", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/el/0/1672", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/ei/1/1673", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA338300169/MONDO:0014222/141/el/0/1672/1674", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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": "CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1672/1674", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/1/1673", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1672", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA338300169/MONDO:0014222/141/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "At least one patient (Patient B.1 in PMID:28414062) with this variant had a phenotype that included recurrent sinopulmonary infections and otitis media (4 pts), lymphoma (1 pt), lymphadenopathy (4 pts), eczema (1 pt), increased circulating antibody levels (0.5 pts), increased proportion of transitional B cells (2 pts), and lymphopenia (1 pt), with genotyping to rule out a variant in PIK3R1, PIK3CG, and PTEN which is highly specific for immunodeficiency 14. Additionally, a phospho-AKT assay in patient T cells revealed over-activation of the PI3K pathway, which was rescued by inhibition using idelalisib (13.5 total points, PMID: 28414062, PP4_Moderate).", "contributionDate": { "date": "2025/12/23", "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": "CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA338300169/MONDO:0014222/141/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.661, which is above the ClinGen Antibody Deficiencies VCEP threshold of >0.644 and predicts a damaging effect on PIK3CD function. The computational predictor CADD gives a PHRED score of 31.0, which is above the ClinGen Antibody Deficiencies VCEP threshold of >25.3 and predicts a deleterious effect on PIK3CD function. The two predictors agree on a damaging effect (PP3).", "contributionDate": { "date": "2025/12/23", "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": "CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA338300169/MONDO:0014222/141/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "This variant is present in gnomAD v4.1.0 at a total combined allele frequency of 0.0000006197, with 1 allele / 1,613,806 total alleles across all populations of gnomAD, which is lower than the ClinGen Antibody Deficiencies VCEP PM2_Supporting threshold of <0.00000132 (PM2_Supporting).", "contributionDate": { "date": "2025/12/23", "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": "CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/el/0/1606", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300169/MONDO:0014222/141/ei/1/1607", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "contributionDate": { "date": "2025/12/23", "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/CA338300169/MONDO:0014222/141/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50095_EP176400614458866", "id": "CG-PCER-AGENT:CG_50095_EP176400614458866", "type": "Agent" }, "comments": "This variant has been reported in at least 2 unrelated probands meeting the VCEP standard for phenotypic criteria, one of whom has a phenotype including lymphoproliferation with splenomegaly (4 pts), hepatic fibrosis and portal hypertension with gastrointestinal bleeding (1 pt), bronchiectasis (4 pts), lymphopenia (1 pt), and decreased IgG (0.5 pts), with genotyping that excluded an alternative basis for disease in PIK3R1 (10.5 pts, PMID:28428270). The other proband has already been counted for PP4_Moderate (PS4_Supporting).", "contributionDate": { "date": "2025/12/23", "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": "CA338300169/MONDO:0014222/141/ci/CA338300169/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1606/1608", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/1/1607", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141/0/1606", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300169/MONDO:0014222/141", "metadata": { "created": "2025-12-23T20:33:09.292Z", "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": "Tue, 23 Dec 2025 20:33:09 -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": "b0b1fd47-57a4-4bc9-be3c-ffee5a993886", "variant": { "@id": "https://reg.genome.network/allele/CA338300169", "id": "CAR:CA338300169", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_005026.5:c.241G>A" } ], "preferred": true } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T00:18:11.708Z" } }, "status": { "code": 200, "name": "OK" } }