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      "label": "ClinGen Lysosomal Storage Disorders Variant Curation Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2",
      "type": "VariantPathogenicityInterpretationGuideline",
      "url": "https://clinicalgenome.org/docs/clingen-lysosomal-storage-disorders-expert-panel-specifications-to-the-acmg-amp-variant-interpretation-guidelines-version-2/",
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    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009290",
      "id": "MONDO:0009290",
      "label": "glycogen storage disease II",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
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            ],
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                "id": "SEPIO:0000329",
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              },
              "id": "0063",
              "label": "PP4",
              "type": "Criterion"
            },
            "evidenceLine": [
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                          "type": "Agent"
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                        "comments": "Two patients with the variant have been reported in the literature, both with late-onset Pompe disease. One had diminished GAA activity, but residual activity was not provided (PMID: 29124014). The second patient had documented laboratory values indicating reduced GAA activity but was also heterozygous for a pseudodeficiency variant. The patient was on enzyme replacement therapy (PMID: 21757382) (PP4). ",
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                    "id": "CA401359804/MONDO:0009290/010/ci/CA401359804/MONDO:0009290/010.002",
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            ],
            "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/1/1634",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/0/1633",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401359804/MONDO:0009290/010/el/0/1636",
        "evidenceItem": [
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            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401359804/MONDO:0009290/010/ei/1/1637",
            "contribution": [
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                  "label": "curator role",
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                "type": "Contribution"
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            ],
            "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/CA401359804/MONDO:0009290/010/el/0/1636/1638",
                "evidenceItem": [
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                    "@id": "CG-PCER:curatorInference/CA401359804/MONDO:0009290/010/ci/CA401359804/MONDO:0009290/010.002",
                    "contribution": [
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                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50009_EP157972030954718",
                          "id": "CG-PCER-AGENT:CG_50009_EP157972030954718",
                          "type": "Agent"
                        },
                        "comments": "This variant is absent in gnomAD v2.1.1 (PM2_Supporting).",
                        "contributionDate": {
                          "date": "2023/4/5",
                          "description": "Date on which this evidence was provided"
                        },
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                      }
                    ],
                    "id": "CA401359804/MONDO:0009290/010/ci/CA401359804/MONDO:0009290/010.002",
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                ],
                "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401359804/MONDO:0009290/010/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401359804/MONDO:0009290/010/ei/1/1718",
            "contribution": [
              {
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                  "description": "Date on which this evidence was provided"
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                  "label": "curator role",
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                },
                "type": "Contribution"
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            ],
            "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/CA401359804/MONDO:0009290/010/el/0/1717/1719",
                "evidenceItem": [
                  {
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                    "contribution": [
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                          "id": "CG-PCER-AGENT:CG_50009_EP157972030954718",
                          "type": "Agent"
                        },
                        "comments": "Two patients are compound heterozygous for the variant and another variant in GAA that has been classified as pathogenic by the ClinGen LD VCEP, including c.1826dup (p.Tyr609Ter) (PMID: 29124014) and c.1935C>A (p.Asp645Gln) (PMID: 21757382). The phase was not confirmed in either case. Totals 2 x 0.5 = 1 point (PM3).",
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                    ],
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                ],
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            ],
            "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/0/1717",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401359804/MONDO:0009290/010/el/0/1594",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401359804/MONDO:0009290/010/ei/1/1595",
            "contribution": [
              {
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                },
                "contributionDate": {
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                  "description": "Date on which this evidence was provided"
                },
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                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0017",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000220",
                "id": "SEPIO:0000220",
                "label": "Pathogenic Very Strong"
              },
              "id": "0017",
              "label": "PVS1",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA401359804/MONDO:0009290/010/el/0/1594/1596",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA401359804/MONDO:0009290/010/ci/CA401359804/MONDO:0009290/010.002",
                    "contribution": [
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                          "id": "CG-PCER-AGENT:CG_50009_EP157972030954718",
                          "type": "Agent"
                        },
                        "comments": "The NM_000152.5:c.2T>C variant in GAA is an initiator codon variant that is predicted to abolish the start codon (p.Met1?). The next in-frame methionine is at position 122 but, even if used, the gene product would be missing the signal sequence (PMID 22252923). This variant results in 3.6% GAA activity in medium and 0% GAA activity in cells and is abnormally synthesized when expressed in HEK293 cells, and is classified as Class B (“potentially less severe”) by Kroos et al, 2012 (PMID: 22644586). PVS1_Strong for initiator codon variant upgraded to PVS1 based on availability of functional evidence (PVS1).",
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                          "description": "Date on which this evidence was provided"
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                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA401359804/MONDO:0009290/010/ci/CA401359804/MONDO:0009290/010.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010/0/1594",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA401359804/MONDO:0009290/010",
    "metadata": {
      "created": "2024-09-28T01:35:28.095Z",
      "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": "Sat, 28 Sep 2024 01:35:27 -0000",
      "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)",
      "version": "2.0.0"
    },
    "statementOutcome": {
      "@id": "https://loinc.org/LA6668-3",
      "id": "LN:LA6668-3",
      "label": "Pathogenic"
    },
    "type": "VariantPathogenicityInterpretation",
    "uuid": "29feb6c3-10a4-4799-9ca8-6c365f460b86",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA401359804",
      "id": "CAR:CA401359804",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000152.5:c.2T>C"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000152.5:c.2T>C"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-11-03T12:44:02.445Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}