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      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "2.3"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010938",
      "id": "MONDO:0010938",
      "label": "T-B+ severe combined immunodeficiency due to JAK3 deficiency",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
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                  "label": "curator role",
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                "type": "Contribution"
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            ],
            "criterion": {
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                "@id": "https://obofoundry.org/sepio/SEPIO:0000220",
                "id": "SEPIO:0000220",
                "label": "Pathogenic Very Strong"
              },
              "id": "0017",
              "label": "PVS1",
              "type": "Criterion"
            },
            "evidenceLine": [
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                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/el/0/1594/1596",
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                        "comments": "c.2350G>A sits at the last nucleotide of exon 17 and was functionally confirmed to disrupt splicing, resulting in skipping of exon 17, as demonstrated by RT-PCR and Sanger sequencing of the resulting cDNA. Exon 17 lies within the functionally important JH1 catalytic kinase domain. Additionally, the out-of-frame deletion of exon 17 introduces a frameshift (p.D784Nfs*60) predicted to undergo NMD (PVS1; PMID: 30177960).",
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                          "label": "curator role",
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                      }
                    ],
                    "id": "CA9301624/MONDO:0010938/121/ci/CA9301624/MONDO:0010938/121.002",
                    "type": "InfFromBkgrndSciKnow"
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                ],
                "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/0/1594",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/el/0/1831",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/ei/1/1832",
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              {
                "agent": {
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                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0018",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "0018",
              "label": "PP4",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/el/0/1831/1833",
                "evidenceItem": [
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                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50091_EP170474596929316",
                          "id": "CG-PCER-AGENT:CG_50091_EP170474596929316",
                          "type": "Agent"
                        },
                        "comments": "t least one SCID patient (PMID: 30177960) underwent SCID panel/whole-exome sequencing, which identified this JAK3 variant in the homozygous state with no alternative explanation (1.0 point). The patient had a family history of SCID, with a sibling who died at 6 months of age with a SCID-like presentation (0.5 point). The patient met SCID diagnostic criteria, with persistently low autologous T cell counts documented from 2 months of age (0.5 point). The patient also presented with a T-B+NK- lymphocyte subset profile confirmed by flow cytometry (0.5 point). A total of 2.5 points were assigned, meeting the PP4_Moderate criterion",
                        "contributionDate": {
                          "date": "2026/9/22",
                          "description": "Date on which this evidence was provided"
                        },
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                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA9301624/MONDO:0010938/121/ci/CA9301624/MONDO:0010938/121.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/0/1831/1833",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/1/1832",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/0/1831",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/ei/1/1637",
            "contribution": [
              {
                "agent": {
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                },
                "contributionDate": {
                  "date": "2026/9/22",
                  "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"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0030",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000329",
                "id": "SEPIO:0000329",
                "label": "Pathogenic Supporting"
              },
              "id": "0030",
              "label": "PM2",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/el/0/1636/1638",
                "evidenceItem": [
                  {
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                    "contribution": [
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                          "id": "CG-PCER-AGENT:CG_50091_EP170474596929316",
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                        },
                        "comments": "The highest population minor allele frequency in gnomAD v4 is 0.00005341 (4/74890 alleles) in African/African American population, which is lower than the ClinGen SCID VCEP threshold (<0.000115) for PM2_Supporting, meeting this criterion (PM2_Supporting).",
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                          "date": "2026/9/22",
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                    ],
                    "id": "CA9301624/MONDO:0010938/121/ci/CA9301624/MONDO:0010938/121.002",
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                ],
                "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/ei/1/1718",
            "contribution": [
              {
                "agent": {
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                  "id": "CG-PCER-AGENT:CG_50091_EP170474596929316",
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                },
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                  "date": "2026/9/22",
                  "description": "Date on which this evidence was provided"
                },
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                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/007",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "007",
              "label": "PM3",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA9301624/MONDO:0010938/121/el/0/1717/1719",
                "evidenceItem": [
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                          "type": "Agent"
                        },
                        "comments": "This variant was found in the homozygous state in 2 SCID patients from 2 unrelated families (PMID: 30177960): one born to consanguineous parents (first-degree cousins, 0.5 point) and one born to non-consanguineous parents (1.0 point). A total of 1.5 points meets the PM3 threshold.\n",
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                          "date": "2026/9/22",
                          "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": "CA9301624/MONDO:0010938/121/ci/CA9301624/MONDO:0010938/121.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/0/1717/1719",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121/0/1717",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA9301624/MONDO:0010938/121",
    "metadata": {
      "created": "2026-10-15T19:02:01.957Z",
      "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, 15 Oct 2026 19:02:01 -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": "2a6c91c9-5b8d-4c8f-b840-b2c238514df2",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA9301624",
      "id": "CAR:CA9301624",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000215.4:c.2350G>A"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000215.4(JAK3):c.2350G>A (p.Asp784Asn)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-28T07:48:29.186Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}