Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002472269 | SCV002769389 | likely pathogenic | Intellectual disability, autosomal dominant 20 | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with MEF2C-related developmental syndrome. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0219 - This variant is non-coding in an alternative transcript. This variant is deep intronic within several RefSeq transcripts (UCSC), however it is within an exon within the transcript most highly expressed in ClinVar. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported in several patients (one confirmed de novo) with MEF2C-related haploinsufficiency syndrome (Decipher, LOVD, PMID: 25131622, PMID: 26633542). (SP) 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 |