{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/ce4d1700-8d2f-43d4-b2db-a351e5aaa75d/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1812056141", "label": "ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CAPN3 Version 2.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0015152", "id": "MONDO:0015152", "label": "autosomal recessive limb-girdle muscular dystrophy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220348/MONDO:0015152/187/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220348/MONDO:0015152/187/ei/1/1685", 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"https://erepo.genome.network/evrepo/api/interpretation/CA220348/MONDO:0015152/187/ei/1/1739", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/4/9", "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/CA220348/MONDO:0015152/187/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220348/MONDO:0015152/187/ci/CA220348/MONDO:0015152/187.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "At least one patient with this variant and a second presumed diagnostic CAPN3 variant displayed progressive limb girdle muscle weakness and absent calpain-3 protein expression, which is highly specific for CAPN3-related LGMD (PP4_Strong; PMID: 18055493, 19556129).", "contributionDate": { "date": "2026/4/9", "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": "CA220348/MONDO:0015152/187/ci/CA220348/MONDO:0015152/187.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220348/MONDO:0015152/187/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220348/MONDO:0015152/187/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220348/MONDO:0015152/187/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220348/MONDO:0015152/187/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220348/MONDO:0015152/187/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/4/9", "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/CA220348/MONDO:0015152/187/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220348/MONDO:0015152/187/ci/CA220348/MONDO:0015152/187.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The filtering allele frequency of this variant is 0.0002367 (the lower threshold of the 95% CI of 308/1179972 exomes and genome chromosomes) in the European (non-Finnish) population in gnomAD v4.1.0, which is less than the ClinGen LGMD VCEP threshold >0.001 for BS1.", "contributionDate": { "date": "2026/4/9", "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": "CA220348/MONDO:0015152/187/ci/CA220348/MONDO:0015152/187.002", "type": "InfFromBkgrndSciKnow" } ], "id": 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"label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220348/MONDO:0015152/187/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220348/MONDO:0015152/187/ci/CA220348/MONDO:0015152/187.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The upper bound of the 95% confidence interval of the Grpmax variant allele frequency in gnomAD v4.1.0 is 0.0002868 (308/1179972 European (non-Finnish) exome and genome chromosomes), which is greater than the ClinGen LGMD VCEP threshold <0.0001 for PM2_Supporting (criterion not met). 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", "contributionDate": { "date": "2026/4/9", "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": "CA220348/MONDO:0015152/187/ci/CA220348/MONDO:0015152/187.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220348/MONDO:0015152/187/0/1669/1671", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220348/MONDO:0015152/187/1/1670", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220348/MONDO:0015152/187/0/1669", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220348/MONDO:0015152/187", "metadata": { "created": "2026-04-09T22:56:36.244Z", "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": "Thu, 09 Apr 2026 22:56:36 -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": "ce4d1700-8d2f-43d4-b2db-a351e5aaa75d", "variant": { "@id": "https://reg.genome.network/allele/CA220348", "id": "CAR:CA220348", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000070.3:c.2393C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000070.3(CAPN3):c.2393C>A (p.Ala798Glu)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-22T20:08:07.548Z" } }, "status": { "code": 200, "name": "OK" } }