{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/4aaaaa8b-632d-4b0d-abb4-999289ba9ca5/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/CA232785/MONDO:0015152/188/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/ei/1/1799", "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/CA232785/MONDO:0015152/188/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA232785/MONDO:0015152/188/ci/CA232785/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 highest population minor allele frequency for this variant is 0.000816 in gnomAD v4.1.10 (73/91068 South Asian chromosomes), which is higher than the VCEP threshold for PM2_Supporting (0.0001) (PM2_Supporting not met).", "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": "CA232785/MONDO:0015152/188/ci/CA232785/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/ei/1/1679", "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/CA232785/MONDO:0015152/188/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA232785/MONDO:0015152/188/ci/CA232785/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 shown to co-segregate with autosomal recessive LGMD in one family member (PMID: 25891276; PP1). ", "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": "CA232785/MONDO:0015152/188/ci/CA232785/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/ei/1/1748", "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/CA232785/MONDO:0015152/188/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA232785/MONDO:0015152/188/ci/CA232785/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 REVEL score is 0.75, which is above the LGMD VCEP threshold of ≥0.70, evidence that correlates with impact to ANO5 function (PP3).", "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": "CA232785/MONDO:0015152/188/ci/CA232785/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/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": "2026/4/9", "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/CA232785/MONDO:0015152/188/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA232785/MONDO:0015152/188/ci/CA232785/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: 21186264, 25891276, 31069529, 38374194; PP4).", "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": "CA232785/MONDO:0015152/188/ci/CA232785/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/el/0/1669", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/ei/1/1670", "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/CA232785/MONDO:0015152/188/el/0/1669/1671", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA232785/MONDO:0015152/188/ci/CA232785/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": "Among a selection of the available literature, this variant has been reported in at least 16 unrelated individuals with features consistent with LGMD or anoctaminopathy (PMID:21186264, 22742934, 23041008, 23663589, 23670307, 25891276, 28187523, 30919934, 31069529, 31517061, 32978841, 34687219, 35563815, 37526466, 31069529, 38374194). \n\nTwo patients had the VOI in a homozygous state without reported familial consanguinity (1.0 pt; PMID: 31069529, 38374194). Three patients were reported as compound heterozygous with the pathogenic variant c.191dup p.(Asn64LysfsTer15) confirmed in trans (1.0 pt x3 = 3.0 pts, PMID: 21186264, 23670307, 25891276) and unknown phase in two patients (0.5 pt x2 = 1.0 pt, PMID: 32978841, 34687219). One patient was reported as compound heterozygous with the pathogenic variant c.1898+1G>A (1.0 pt, PMID: 28187523) (PM3_Very Strong).\n\nc.191dup p.(Asn64LysfsTer15) is predicted on a different haplotype than the curated variant", "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": "CA232785/MONDO:0015152/188/ci/CA232785/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1669/1671", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/1/1670", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1669", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/ei/1/1778", "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/CA232785/MONDO:0015152/188/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA232785/MONDO:0015152/188/ci/CA232785/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 filtering allele frequency for this variant is 0.0006536 in gnomAD v.4.1.0 (the lower threshold of the 95% CI of 73/91068 South Asian chromosomes), which is less than the LGMD VCEP threshold for BA1 (BA1 not met).", "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": "CA232785/MONDO:0015152/188/ci/CA232785/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA232785/MONDO:0015152/188/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/CA232785/MONDO:0015152/188/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA232785/MONDO:0015152/188/ci/CA232785/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 filtering allele frequency for this variant is 0.0006536 in gnomAD v.4.1.0 (the lower threshold of the 95% CI of 73/91068 South Asian chromosomes), which is less than the LGMD VCEP threshold for BA1 (BS1 not met).", "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": "CA232785/MONDO:0015152/188/ci/CA232785/MONDO:0015152/188.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188/0/1804", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA232785/MONDO:0015152/188", "metadata": { "created": "2026-04-09T22:34:09.605Z", "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 22:33:49 -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": "4aaaaa8b-632d-4b0d-abb4-999289ba9ca5", "variant": { "@id": "https://reg.genome.network/allele/CA232785", "id": "CAR:CA232785", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_213599.3:c.1733T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_213599.3(ANO5):c.1733T>C (p.Phe578Ser)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T20:18:08.329Z" } }, "status": { "code": 200, "name": "OK" } }