| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intellectual disability syndromic and non-syndromic v1.373 | MDGA2 |
Zornitza Stark gene: MDGA2 was added gene: MDGA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: MDGA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MDGA2 were set to https://doi.org/10.1101/2025.08.28.25330873; 40168357; 27608760 Phenotypes for gene: MDGA2 were set to MDGA2-related neurodevelopmental disorder MONDO:0700092 Review for gene: MDGA2 was set to GREEN Added comment: Affected individuals present with a broad neurodevelopmental impairment-like phenotype. Pre-print - https://doi.org/10.1101/2025.08.28.25330873 Individuals with developmental and epileptic encephalopathy (DEE) 8 individuals from 6 consanguineous families exhibiting infantile hypotonia, severe neurodevelopmental delay, intractable seizures, progressive brain atrophy, and consistent dysmorphic features. 7 different biallelic LoF variants were identified p.Tyr913Ter, p.Arg404Ter, p.Leu920Ter, c.421-1G>A, p.Lys391SerfsTer7 and c.421-96_595+99del - all variants are rare or absent in gnomAD v4.1 In vitro functional studies of three nonsense variants in mammalian expression systems and hippocampal cultured neurons that resulted in impaired MDGA2 membrane trafficking are supportive of a loss-of-function mechanism. PMID: 40168357, 27608760 A knockout mouse model showed that MGAD2-deficient mice presented with autism-like behaviours (social deficits, repetitive behaviour, and cognitive impairment). The mice also showed abnormalities in excitatory synapses. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.50 | MGA | Zornitza Stark Classified gene: MGA as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.50 | MGA | Zornitza Stark Gene: mga has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.49 | MGA | Zornitza Stark edited their review of gene: MGA: Added comment: Note LoF variants now also associated with POF, supportive mouse model. Downgrade to Amber until further delineation of phenotypes and mechanisms.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.11 | MGA | Zornitza Stark Marked gene: MGA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.11 | MGA | Zornitza Stark Gene: mga has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.11 | MGA | Zornitza Stark Classified gene: MGA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.11 | MGA | Zornitza Stark Gene: mga has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v1.10 | MGA |
Zornitza Stark gene: MGA was added gene: MGA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: MGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MGA were set to 39600096; 20044811 Phenotypes for gene: MGA were set to Syndromic disease, MONDO:0002254, MGA-related Review for gene: MGA was set to GREEN Added comment: Three individuals with de novo LoF variants reported in individuals with ID and congenital anomalies. Zebrafish model supports role of this transcription factor in organogenesis. Note there are previous, less clear reports of association with NDD/CHD. Gene is constrained for LoF variants in gnomad v4; however, note there are ~30 individuals with LoF variants present. Borderline Green/Amber. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.6883 | OPA3 | Zornitza Stark Phenotypes for gene: OPA3 were changed from to 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR; Optic atrophy 3 with cataract (MIM#165300), AD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.6248 | OPA3 | Chirag Patel reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25159689, 31119193, 31928268; Phenotypes: 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR, Optic atrophy 3 with cataract (MIM#165300), AD; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3323 | MGAT2 | Zornitza Stark Marked gene: MGAT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3323 | MGAT2 | Zornitza Stark Gene: mgat2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3323 | MGAT2 | Zornitza Stark Phenotypes for gene: MGAT2 were changed from to Congenital disorder of glycosylation, type IIa, MIM# 212066; MGAT2-CDG, MONDO:0008908 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3322 | MGAT2 | Zornitza Stark Publications for gene: MGAT2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3321 | MGAT2 | Zornitza Stark Mode of inheritance for gene: MGAT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.3320 | MGAT2 | Zornitza Stark reviewed gene: MGAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8808595, 11228641, 22105986, 33044030, 31420886; Phenotypes: Congenital disorder of glycosylation, type IIa, MIM# 212066, MGAT2-CDG, MONDO:0008908; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v0.0 | MGAT2 |
Zornitza Stark gene: MGAT2 was added gene: MGAT2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: MGAT2 was set to Unknown |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||