{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/6f0d42f5-587e-4b7c-a76d-9a83877e909a/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1812076188", "label": "ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ANO5 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "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/CA10606240/MONDO:0015152/188/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10606240/MONDO:0015152/188/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/7/8", "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/CA10606240/MONDO:0015152/188/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10606240/MONDO:0015152/188/ci/CA10606240/MONDO:0015152/188.002", "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 reported with this variant and a second presumed diagnostic ANO5 variant had a clinical suspicion of LGMD (PMID: 30564623; LOVD Individual #00221640) (PP4).", "contributionDate": { "date": "2025/7/8", "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": "CA10606240/MONDO:0015152/188/ci/CA10606240/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10606240/MONDO:0015152/188/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10606240/MONDO:0015152/188/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/7/8", "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/CA10606240/MONDO:0015152/188/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10606240/MONDO:0015152/188/ci/CA10606240/MONDO:0015152/188.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/7/8", "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": "CA10606240/MONDO:0015152/188/ci/CA10606240/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10606240/MONDO:0015152/188/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10606240/MONDO:0015152/188/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/7/8", "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/CA10606240/MONDO:0015152/188/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10606240/MONDO:0015152/188/ci/CA10606240/MONDO:0015152/188.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The NM_213599.3: c.108_109del p.(Glu36AspfsTer7) variant in ANO5 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 3/22, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1).", "contributionDate": { "date": "2025/7/8", "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": "CA10606240/MONDO:0015152/188/ci/CA10606240/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10606240/MONDO:0015152/188/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10606240/MONDO:0015152/188/ei/1/1610", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2025/7/8", "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/CA10606240/MONDO:0015152/188/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10606240/MONDO:0015152/188/ci/CA10606240/MONDO:0015152/188.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "This variant has been identified in at least two patients with features consistent with ANO5-related muscle disease (PMID: 32367299, 39666917, 30564623; LOVD Individuals #00460288, #00221640), including in unknown phase with a pathogenic ANO5 variant in one patient with hyperCKemia, signs of myopathy on EMG, mitochondrial signs on muscle biopsy, and typical changes on muscle MRI (c.191dup p.(Asn64LysfsTer15), 0.5 pts, PMID: 32367299, 39666917; LOVD Individual #00460288) (PM3_Supporting).\n\nCannot check co-occurrence data since variant under curation is absent from gnomAD.", "contributionDate": { "date": "2025/7/8", "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": "CA10606240/MONDO:0015152/188/ci/CA10606240/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188/0/1609", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10606240/MONDO:0015152/188", "metadata": { "created": "2025-07-08T18:22:27.807Z", "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, 08 Jul 2025 18:22:27 -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": "6f0d42f5-587e-4b7c-a76d-9a83877e909a", "variant": { "@id": "https://reg.genome.network/allele/CA10606240", "id": "CAR:CA10606240", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_213599.3:c.108_109del" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_213599.3(ANO5):c.108_109del (p.Glu36fs)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-29T06:03:11.964Z" } }, "status": { "code": 200, "name": "OK" } }