{
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      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1535438831",
      "label": "ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA2 Version 1.1.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "1.1.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0700269",
      "id": "MONDO:0700269",
      "label": "BRCA2-related cancer predisposition",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
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        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025281/MONDO:0700269/097/el/0/1636",
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                  "label": "curator role",
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                "type": "Contribution"
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            ],
            "evidenceLine": [
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                          "type": "Agent"
                        },
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                        "contributionDate": {
                          "date": "2025/8/18",
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                          "label": "curator role",
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                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA025281/MONDO:0700269/097/ci/CA025281/MONDO:0700269/097.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/0/1636",
        "type": "EvidenceLine"
      },
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        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025281/MONDO:0700269/097/el/0/1828",
        "evidenceItem": [
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                  "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/8/18",
                  "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/CA025281/MONDO:0700269/097/el/0/1828/1830",
                "evidenceItem": [
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                    "@id": "CG-PCER:curatorInference/CA025281/MONDO:0700269/097/ci/CA025281/MONDO:0700269/097.002",
                    "contribution": [
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                          "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                          "type": "Agent"
                        },
                        "comments": "Intronic variant, functional data considered only from assays that measure effect via mRNA and protein. Reported by two calibrated studies incorporating mRNA splicing effects to exhibit protein function similar to pathogenic control variants (PMIDs:39779857, 39779848) (PS3 met).",
                        "contributionDate": {
                          "date": "2025/8/18",
                          "description": "Date on which this evidence was provided"
                        },
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                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
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                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA025281/MONDO:0700269/097/ci/CA025281/MONDO:0700269/097.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/0/1828/1830",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/1/1829",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/0/1828",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025281/MONDO:0700269/097/el/0/1762",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA025281/MONDO:0700269/097/ei/1/1763",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50087_EP169680482377844",
                  "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/8/18",
                  "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/CA025281/MONDO:0700269/097/el/0/1762/1764",
                "evidenceItem": [
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                    "contribution": [
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                          "id": "CG-PCER-AGENT:CG_50087_EP169680482377844",
                          "type": "Agent"
                        },
                        "comments": "This variant is reported to result in aberrant mRNA splicing. Mini-gene assays demonstrated that the variant impacts splicing by skipping of exon 16 (75.3%), utilization of cryptic donor sites 100 bp upstream in exon 16 (13.3%), and retention of 20 bp from intron 16 (3.8%) resulting in >90% of transcripts leading to a frameshift and generating a premature stop codon (PMID: 29881398). Appropriate code strength was determined by comparison of results to PVS1 decision tree with PVS1 (RNA) downgraded to PVS1_Strong (RNA). ",
                        "contributionDate": {
                          "date": "2025/8/18",
                          "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": "CA025281/MONDO:0700269/097/ci/CA025281/MONDO:0700269/097.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/0/1762/1764",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/1/1763",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097/0/1762",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA025281/MONDO:0700269/097",
    "metadata": {
      "created": "2025-08-18T00:42:32.531Z",
      "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": "Mon, 18 Aug 2025 00:42:32 -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": "6d965a38-858f-499a-ae39-bc0521500627",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA025281",
      "id": "CAR:CA025281",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000059.4:c.7805+3A>C"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000059.4(BRCA2):c.7805+3A>C"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-13T20:50:29.915Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}