| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Blepharophimosis v0.28 | SMARCA2 | Zornitza Stark Phenotypes for gene: SMARCA2 were changed from Blepharophimosis-intellectual disability syndrome (BIS) to Blepharophimosis-intellectual disability syndrome (BIS), MIM#619293 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Blepharophimosis v0.15 | SMARCA2 | Zornitza Stark Marked gene: SMARCA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Blepharophimosis v0.15 | SMARCA2 | Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Blepharophimosis v0.15 | SMARCA2 | Zornitza Stark Classified gene: SMARCA2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Blepharophimosis v0.15 | SMARCA2 | Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Blepharophimosis v0.14 | SMARCA2 |
Konstantinos Varvagiannis gene: SMARCA2 was added gene: SMARCA2 was added to Blepharophimosis. Sources: Literature Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMARCA2 were set to 32694869 Phenotypes for gene: SMARCA2 were set to Blepharophimosis-intellectual disability syndrome (BIS) Penetrance for gene: SMARCA2 were set to Complete Mode of pathogenicity for gene: SMARCA2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: SMARCA2 was set to GREEN Added comment: Cappuccio et al (2020 - PMID: 32694869) report on individuals with de novo SMARCA2 variants with features of a novel, blepharophimosis-intellectual disability syndrome (BIS) but whose clinical presentation did not fit a diagnosis of Nicolaides-Baraitser (NB) syndrome. Clinical details on 14 subjects with BIS were provided, DD/ID being a universal feature (14/14 - moderate to severe ID). Compared to other syndromes with blepharophimosis, lack of ptosis (observed in only 14% in this cohort), epicanthus inversus and limb abnormalities were proposed to distinguish BIS from other recognizable syndromes with blepharophimosis. All individuals with BIS were found to harbor de novo missense variants. These clustered outside the helicase domain and localized within exons 8,9 and 19. Few (6) additional individuals with de novo missense variants (in ex. 8, 14, 19) did not fit either diagnosis (NB or BIS) with the SNVs classified as VUS. According to Cappuccio et al, most individuals with diagnosis of NB syndrome harbor variants spanning exons 15 to 25 [corresponding to the ATPase domain, which in turn is split in a Helicase ATP-Binding domain (720-912) and a helicase C-terminal domain (1080-1164)]. Most NB-associated variants are missense and rarely in-frame exon deletions. As also commented on CNVs (deletions or duplications) encompassing SMARCA2 have been reported in individuals with DD/ID although these did not fit a diagnosis of NB syndrome (and CNVs were rather not intragenic/limited to SMARCA2) [cited PMIDs: 31530938, 28846756]. Transcriptomic and methylation signatures confirmed molecular stratification of affected individuals with SMARCA2-related disorders (and controls). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||