Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002272935 | SCV002557415 | likely pathogenic | Developmental and epileptic encephalopathy, 11 | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with SCN2A-related disorders. Variants causing a gain of function result in either developmental and epileptic encephalopathy 11 (MIM#613721) or benign familial infantile seizures 3 (MIM#607745), whereas variants displaying a loss of function cause austism spectrum disorder and/or intellectual disability, with or without childhood-onset seizures; the functional consequence of truncating variants is unknown (OMIM, PMID: 29691040). 0107 - This gene is associated with autosomal dominant disease. (I) 0213 - In-frame deletion in a non-repetitive region that has high conservation. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0600 - Variant partially overlaps the annotated ion transport domain (DECIPHER). (I) 0705 - No comparable in frame deletion variants in the deleted region have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |