{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/43b1324a-d892-4f96-933f-2aa736c2f75b/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1807907463", "label": "ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DYSF 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/CA1705669/MONDO:0015152/180/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/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": "2026/4/10", "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/CA1705669/MONDO:0015152/180/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "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 threshold of the 95% CI of the Grpmax variant allele frequency is 0.0001051 in gnomAD v4.1.0 (3/73748 African/African American chromosomes), which is greater than the ClinGen LGMD VCEP threshold for PM2_Supporting (<0.0001). ", "contributionDate": { "date": "2026/4/10", "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": "CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/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": "2026/4/10", "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/CA1705669/MONDO:0015152/180/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "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_003494.4: c.1178_1180+4dup variant in DYSF, which is also known as NM_001130987.2: c.1274_1276+4dup, is a duplication of 7 nucleotides spanning the boundary between exon 12 and intron 12, causing exon 12 to be extended by 7 bp and resulting in a frameshift and premature truncation, p.(Met394SerfsTer20), with nonsense mediated decay expected (PVS1). \n\nWhile the GT is maintained at the original +1,2 dinucleotide positions in the presence of the duplication, the dup alters the sequence at the original exon-intron boundary via replacement of the GT at the +5/6 position with AG. This alteration completely ablates the splice donor site at the original exon-intron boundary (GENEie gives 3 NIF 0 windows). The now-shifted splice donor sequence following the extended exon is thus expected to be used, shifting the reading frame and introducing a PTC. VEP annotates this variant as a frameshift (see gnomAD).", "contributionDate": { "date": "2026/4/10", "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": "CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/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": "2026/4/10", "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/CA1705669/MONDO:0015152/180/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The Grpmax FAF (the lower bound of the 95% confidence interval of the maximum credible genetic ancestry group allele frequency) is 0.00001009, which is less than the ClinGen LGMD VCEP threshold for BS1 (>0.001)", "contributionDate": { "date": "2026/4/10", "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": "CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/ei/1/1655", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/4/10", "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/CA1705669/MONDO:0015152/180/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/4/10", "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": "CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1654", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/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": "2026/4/10", "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/CA1705669/MONDO:0015152/180/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "PVS1 applied", "contributionDate": { "date": "2026/4/10", "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": "CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/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": "2026/4/10", "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/CA1705669/MONDO:0015152/180/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "Only observed as a single hit", "contributionDate": { "date": "2026/4/10", "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": "CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1705669/MONDO:0015152/180/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/4/10", "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/CA1705669/MONDO:0015152/180/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "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 observed in a heterozygous state in two patients with a clinical suspicion of LGMD or muscular dystrophy, including one with a complete absence of dysferlin immunostaining in skeletal muscle. However, no second allele was identified in either case (PMID: 18832576, 30564623; LOVD Individual 00222254) (PM3 not met).", "contributionDate": { "date": "2026/4/10", "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": "CA1705669/MONDO:0015152/180/ci/CA1705669/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA1705669/MONDO:0015152/180", "metadata": { "created": "2026-04-10T19:19:49.378Z", "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": "Fri, 10 Apr 2026 19:19:49 -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": "43b1324a-d892-4f96-933f-2aa736c2f75b", "variant": { "@id": "https://reg.genome.network/allele/CA1705669", "id": "CAR:CA1705669", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001130987.2:c.1274_1276+4dup" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001130987.2(DYSF):c.1274_1276+4dup" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-05T14:48:45.443Z" } }, "status": { "code": 200, "name": "OK" } }