{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/5f8f545e-ffe9-4fce-bb11-c491e1dcf329/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 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/CA224408/MONDO:0015152/188/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/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": "2026/2/17", "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/CA224408/MONDO:0015152/188/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA224408/MONDO:0015152/188/ci/CA224408/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 with this variant and a second presumed diagnostic ANO5 allele displayed a progressive limb girdle pattern of muscle weakness (PMID: 26809617, 31353849, 20096397; PP4).", "contributionDate": { "date": "2026/2/17", "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": "CA224408/MONDO:0015152/188/ci/CA224408/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/MONDO:0015152/188/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/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": "2026/2/17", "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/CA224408/MONDO:0015152/188/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA224408/MONDO:0015152/188/ci/CA224408/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 upper bound of the 95% confidence interval of the Grpmax variant allele frequency in gnomAD v4.1.0 is 0.000021617 (17/1179582 European (non-Finnish) chromosomes), which is less than the threshold of 0.0001 for PM2_Supporting, meeting this criterion (PM2_Supporting).\n", "contributionDate": { "date": "2026/2/17", "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": "CA224408/MONDO:0015152/188/ci/CA224408/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/MONDO:0015152/188/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/MONDO:0015152/188/ei/1/1649", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/2/17", "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/CA224408/MONDO:0015152/188/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA224408/MONDO:0015152/188/ci/CA224408/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 also been reported to co-segregate with autosomal recessive LGMD in four affected family members from two families sharing the same haplotype (PMID: 20096397; PP1_Strong).\n\nBoth families had an individual over 60 years who was homozygous for the variant and reporting no symptoms. However, raised CK and mild iliopsoas weakness (MRC <5) was identified in both individuals on exam, and they were described as 'affected' multiple times in paper. For these reasons, we opted to include these individuals as segregations.", "contributionDate": { "date": "2026/2/17", "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": "CA224408/MONDO:0015152/188/ci/CA224408/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/MONDO:0015152/188/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/MONDO:0015152/188/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/2/17", "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/CA224408/MONDO:0015152/188/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA224408/MONDO:0015152/188/ci/CA224408/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 reported in at least five unrelated individuals with features consistent with LGMD (PMID: 26809617, 31353849, 20096397), including in a homozygous state in the probands of two consanguineous families sharing a common haplotype (0.25 pts x2; PMID: 20096397) and in unknown phase with a pathogenic variant in three affected individuals (c.989dupT p.(Leu330Phefs), 0.5 pts, PMID: 26809617; c.191dupA p.(Asn64LysfsTer15), 0.5 pts, PMID: 31353849; and c.2272C>T p.(Arg758Cys), 0.5 pts, PMID: 31353849) (PM3_Strong).", "contributionDate": { "date": "2026/2/17", "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": "CA224408/MONDO:0015152/188/ci/CA224408/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/MONDO:0015152/188/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA224408/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": "2026/2/17", "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/CA224408/MONDO:0015152/188/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA224408/MONDO:0015152/188/ci/CA224408/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": "RNA analysis has demonstrated a complete splice effect of this variant, resulting in the deletion of the last 38 nucleotides of exon 13, which is expected to lead to a frameshift, premature truncation, p.(Ala432GlyfsTer49), and subsequent nonsense mediated decay (PMID: 20096397, PVS1_RNA).", "contributionDate": { "date": "2026/2/17", "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": "CA224408/MONDO:0015152/188/ci/CA224408/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188/0/1594", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA224408/MONDO:0015152/188", "metadata": { "created": "2026-02-17T20:02:03.229Z", "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, 17 Feb 2026 20:02:03 -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": "5f8f545e-ffe9-4fce-bb11-c491e1dcf329", "variant": { "@id": "https://reg.genome.network/allele/CA224408", "id": "CAR:CA224408", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_213599.3:c.1295C>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_213599.3(ANO5):c.1295C>G (p.Ala432Gly)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T04:20:25.373Z" } }, "status": { "code": 200, "name": "OK" } }