Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV001542428 | SCV001761130 | uncertain significance | Kleefstra syndrome 2 | 2020-06-26 | criteria provided, single submitter | clinical testing | The inherited 349 kb duplication results in duplication of the first 38 exons (of 59) of the KMT2C gene. The majority of pathogenic variants in KMT2C are nonsense or frameshift [3,4], suggesting loss-of-function is the likely mechanism of disease. Moreover, ClinGen Dosage Sensitivity curation [5] indicates that the KMT2C gene has haploinsufficiency score of 3 (i.e. sufficient evidence for haploinsufficiency) whereas triplosensitivity score is zero (i.e., no evidence for triplosensitivity). There are no additional protein coding genes located within this duplication. Based on the available evidence, the 349 kb duplication inherited from an asymptomatic parent is assessed as a variant of uncertain significance. |