{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/1966b172-cd67-49e8-8831-ce85e822c8a4/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/CA426697783/MONDO:0015152/180/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/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": "2026/5/7", "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/CA426697783/MONDO:0015152/180/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA426697783/MONDO:0015152/180/ci/CA426697783/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": "While this variant was identified in a Jain Foundation Dysferlin Registry participant who had disease range dysferlin in blood monocytes (Jain Foundation Dysferlin Registry internal data communication), the clinical phenotype of this individual was not confirmed, and they were also heterozygous for two other DYSF variants with more evidence for pathogenicity: c.937+4A>T, which ablates canonical donor (curation in progress) and c.2779delG p.(Ala927LeufsTer21), classified as Pathogenic. This variant is not present in gnomAD v2 exomes, and so co-occurrence with the other variants identified in this individual cannot be assessed. \n\nEmory (Eurofins) is only submitter in ClinVar. Case from Nallamilli 2018 (Emory) is only case in LOVD. No other literature or cases identified. ", "contributionDate": { "date": "2026/5/7", "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": "CA426697783/MONDO:0015152/180/ci/CA426697783/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/el/0/1579", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/ei/1/1580", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/5/7", "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/CA426697783/MONDO:0015152/180/el/0/1579/1581", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA426697783/MONDO:0015152/180/ci/CA426697783/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": "Found in a heterozygous state, phase unknown, with two other DYSF variants, one classified as pathogenic by the VCEP and the other a splice region variant predicted to ablate the canonical donor site (Jain Foundation Dysferlin Registry internal data communication).\n\nWe do not include this code in our specifications. ", "contributionDate": { "date": "2026/5/7", "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": "CA426697783/MONDO:0015152/180/ci/CA426697783/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1579/1581", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/1/1580", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1579", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/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": "2026/5/7", "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/CA426697783/MONDO:0015152/180/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA426697783/MONDO:0015152/180/ci/CA426697783/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.438T>C p.(Pro146=) variant in DYSF, which is also known as NM_001130987.2: c.441T>C p.(Pro147=), is a synonymous variant that is not expected to affect the protein amino acid sequence. It is not located in a splice region and is not predicted to affect splicing (SpliceAI score 0) (BP4, BP7). ", "contributionDate": { "date": "2026/5/7", "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": "CA426697783/MONDO:0015152/180/ci/CA426697783/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1654", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/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": "2026/5/7", "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/CA426697783/MONDO:0015152/180/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA426697783/MONDO:0015152/180/ci/CA426697783/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": "While this variant was identified in a Jain Foundation Dysferlin Registry participant who had disease range dysferlin in blood monocytes (Jain Foundation Dysferlin Registry internal data communication), the clinical phenotype of this individual was not confirmed, and they were also heterozygous for two other DYSF variants with more evidence for pathogenicity. ", "contributionDate": { "date": "2026/5/7", "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": "CA426697783/MONDO:0015152/180/ci/CA426697783/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/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": "2026/5/7", "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/CA426697783/MONDO:0015152/180/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA426697783/MONDO:0015152/180/ci/CA426697783/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 is absent from gnomAD v4.1.0 genomes but fails quality filters in exomes (PM2_Supporting).", "contributionDate": { "date": "2026/5/7", "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": "CA426697783/MONDO:0015152/180/ci/CA426697783/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/5/7", "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/CA426697783/MONDO:0015152/180/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA426697783/MONDO:0015152/180/ci/CA426697783/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.438T>C p.(Pro146=) variant in DYSF, which is also known as NM_001130987.2: c.441T>C p.(Pro147=), is a synonymous variant that is not expected to affect the protein amino acid sequence. It is not located in a splice region and is not predicted to affect splicing (SpliceAI score 0) (BP4, BP7). ", "contributionDate": { "date": "2026/5/7", "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": "CA426697783/MONDO:0015152/180/ci/CA426697783/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/el/0/1597", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA426697783/MONDO:0015152/180/ei/1/1598", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/5/7", "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/CA426697783/MONDO:0015152/180/el/0/1597/1599", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA426697783/MONDO:0015152/180/ci/CA426697783/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": "Found in a heterozygous state with two other DYSF variants, one classified as pathogenic by the VCEP and the other a splice region variant predicted to ablate the canonical donor site (Jain Foundation Dysferlin Registry internal data communication), but phase was not confirmed. This variant is not present in gnomAD v2 exomes, and so co-occurrence with the other variants identified in this individual cannot be assessed. \n", "contributionDate": { "date": "2026/5/7", "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": "CA426697783/MONDO:0015152/180/ci/CA426697783/MONDO:0015152/180.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1597/1599", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/1/1598", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180/0/1597", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA426697783/MONDO:0015152/180", "metadata": { "created": "2026-05-07T15:03:38.699Z", "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, 07 May 2026 15:03:38 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26334-5", "id": "LN:LA26334-5", "label": "Likely Benign" }, "type": "VariantPathogenicityInterpretation", "uuid": "1966b172-cd67-49e8-8831-ce85e822c8a4", "variant": { "@id": "https://reg.genome.network/allele/CA426697783", "id": "CAR:CA426697783", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001130987.2:c.441T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001130987.2(DYSF):c.441T>C (p.Pro147=)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T06:57:58.781Z" } }, "status": { "code": 200, "name": "OK" } }