{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/42475cad-a762-4c93-ac2f-2f516266eb17/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/CA338300460/MONDO:0014222/141/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/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/CA338300460/MONDO:0014222/141/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300460/MONDO:0014222/141/ci/CA338300460/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": "Cultured cells exogenously expressing the variant exhibit higher phospho-AKT (Ser473) signal relative to control cells (PMID: 28428270, PMID: 28414062). Lipid kinase phosphorylation signal associated with the variant was 10-fold to 15-fold higher than wild-type (PMID: 28414062). Hydrogen deuterium exchange mass spectrometry also showed increased exchange at the interfaces between the variant and PIK3R1 (PMID: 28414062, PS3_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": "CA338300460/MONDO:0014222/141/ci/CA338300460/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/MONDO:0014222/141/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/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/CA338300460/MONDO:0014222/141/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300460/MONDO:0014222/141/ci/CA338300460/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 0.244, which is below the ClinGen Antibody Deficiencies VCEP threshold of >0.644 and does not predict a damaging effect on PIK3CD function. The computational predictor CADD gives a PHRED score of 32, which is above the ClinGen Antibody Deficiencies VCEP threshold of >25.3 and predicts a deleterious effect on PIK3CD function. Because the two predictors do not agree on a damaging effect, PP3 is not met.", "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": "CA338300460/MONDO:0014222/141/ci/CA338300460/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/MONDO:0014222/141/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/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/CA338300460/MONDO:0014222/141/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300460/MONDO:0014222/141/ci/CA338300460/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 absent from gnomAD v4.1.0 (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": "CA338300460/MONDO:0014222/141/ci/CA338300460/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/MONDO:0014222/141/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/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/CA338300460/MONDO:0014222/141/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300460/MONDO:0014222/141/ci/CA338300460/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 proband harboring this variant had a phenotype that included recurrent sinopulmonary infections including severe pneumonia and bronchiectasis (4 pts), lymphadenopathy and lymphadenitis (4 pts), Epstein-Barr virus infection, plantar warts (3 pts), decreased proportion of naive CD4 T cells, and reduced antibody responses to multiple vaccines, as well as markedly increased phospho-AKT levels in the patient's T cells, with genotyping by whole exome sequencing that did not identify an alternative basis for disease in the PIK3R1 gene, which together are highly specific for immunodeficiency 14 (11 total pts, 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": "CA338300460/MONDO:0014222/141/ci/CA338300460/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/MONDO:0014222/141/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/MONDO:0014222/141/ei/1/1685", "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/CA338300460/MONDO:0014222/141/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300460/MONDO:0014222/141/ci/CA338300460/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": "CA338300460/MONDO:0014222/141/ci/CA338300460/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/MONDO:0014222/141/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA338300460/MONDO:0014222/141/ei/1/1700", "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/CA338300460/MONDO:0014222/141/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA338300460/MONDO:0014222/141/ci/CA338300460/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 3 apparently unrelated probands meeting the VCEP standard for phenotypic criteria. In all three cases, the probands exceeded 6 phenotypic points with genotyping that excluded causes in other loci. One proband had already been counted for the PP4_Moderate code (PS4_Moderate; PMID: 28414062, PMID: 28428270). The two other patients had CD4+ lymphopenia (1 pt), infantile onset, and adenoidectomy (1 pt) combined in one case with recurrent otitis media and sinusitis (4 pts), high IgM serum levels (0.5 pts, low serum IgG2 and IgG4 (0.5 pts), and decreased memory B cells (1 pt), and in the other case with splenomegaly and lymphadenopathy (4 pts), growth retardation (0.5 pts), elevated transitional B cells (2 pts), and reduced IgA. Both patients were genotyped by next-generation sequencing panel for primary immunodeficiencies (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": "CA338300460/MONDO:0014222/141/ci/CA338300460/MONDO:0014222/141.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141/0/1699", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA338300460/MONDO:0014222/141", "metadata": { "created": "2025-12-23T20:40:00.980Z", "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 20:40:00 -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": "42475cad-a762-4c93-ac2f-2f516266eb17", "variant": { "@id": "https://reg.genome.network/allele/CA338300460", "id": "CAR:CA338300460", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_005026.5:c.371G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_005026.5:c.371G>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T15:40:04.403Z" } }, "status": { "code": 200, "name": "OK" } }