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Intellectual disability syndromic and non-syndromic v0.3381 CELF2 Zornitza Stark Gene: celf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3381 CELF2 Zornitza Stark Classified gene: CELF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3381 CELF2 Zornitza Stark Gene: celf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3380 CELF2 Zornitza Stark gene: CELF2 was added
gene: CELF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CELF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELF2 were set to 33131106
Phenotypes for gene: CELF2 were set to Developmental and epileptic encephalopathy
Review for gene: CELF2 was set to GREEN
Added comment: Five unrelated individuals reported. Four with de novo variants, and one inherited from a mosaic mother. Notably, all identified variants, except for c.272‐1G>C, were clustered within 20 amino acid residues of the C‐terminus, which might be a nuclear localization signal.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3379 FGF13 Zornitza Stark Marked gene: FGF13 as ready
Intellectual disability syndromic and non-syndromic v0.3379 FGF13 Zornitza Stark Gene: fgf13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3379 FGF13 Zornitza Stark Classified gene: FGF13 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3379 FGF13 Zornitza Stark Gene: fgf13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3378 FGF13 Zornitza Stark gene: FGF13 was added
gene: FGF13 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FGF13 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FGF13 were set to 33245860
Phenotypes for gene: FGF13 were set to Intellectual disability; epilepsy
Mode of pathogenicity for gene: FGF13 was set to Other
Review for gene: FGF13 was set to GREEN
Added comment: Two sibling pairs and three unrelated males reported who presented in infancy with intractable focal seizures and severe developmental delay. The variants were located in the N-terminal domain of the A isoform of FGF13/FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3377 UBR7 Zornitza Stark Marked gene: UBR7 as ready
Intellectual disability syndromic and non-syndromic v0.3377 UBR7 Zornitza Stark Gene: ubr7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3377 UBR7 Zornitza Stark Classified gene: UBR7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3377 UBR7 Zornitza Stark Gene: ubr7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3376 UBR7 Zornitza Stark gene: UBR7 was added
gene: UBR7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UBR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBR7 were set to 33340455
Phenotypes for gene: UBR7 were set to Intellectual disability; epilepsy; hypothyroidism; congenital anomalies; dysmorphic features
Review for gene: UBR7 was set to GREEN
Added comment: Seven individuals from 6 unrelated families. All had developmental delay, and all males had urogenital anomalies, namely cryptorchidism in 5/6 and small penis in 1/6. Six individuals had seizures and hypotonia. Hypothyroidism was present in 4/7 individuals, and ptosis was noted in 6/7 individuals. Five individuals exhibited cardiac abnormalities: two had ventricular septal defect, one had atrial septal defect, one had a patent ductus arteriosus requiring surgery, and the other had a patent ductus arteriosus and a patent foramen ovale that both closed spontaneously. Five individuals had short stature (height < 3rd percentile). Physical examination revealed various dysmorphic features, including prominent forehead (3/7), hypertelorism (4/7), telecanthus (1/7), epicanthus(1/7), downslanting palpebral fissures (3/7), thick eyebrow (1/7), low-set ears (3/7), long philtrum (2/7), unilateral single transverse palmar crease (1/7), and hypertrichosis (1/7).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3375 RALGAPB Zornitza Stark Marked gene: RALGAPB as ready
Intellectual disability syndromic and non-syndromic v0.3375 RALGAPB Zornitza Stark Gene: ralgapb has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3375 RALGAPB Zornitza Stark Classified gene: RALGAPB as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3375 RALGAPB Zornitza Stark Gene: ralgapb has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3374 RNU7-1 Zornitza Stark Marked gene: RNU7-1 as ready
Intellectual disability syndromic and non-syndromic v0.3374 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3374 RNU7-1 Zornitza Stark Classified gene: RNU7-1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3374 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3373 LSM11 Zornitza Stark Marked gene: LSM11 as ready
Intellectual disability syndromic and non-syndromic v0.3373 LSM11 Zornitza Stark Gene: lsm11 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3373 LSM11 Zornitza Stark Classified gene: LSM11 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3373 LSM11 Zornitza Stark Gene: lsm11 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3372 DPH2 Zornitza Stark Marked gene: DPH2 as ready
Intellectual disability syndromic and non-syndromic v0.3372 DPH2 Zornitza Stark Gene: dph2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3372 DPH2 Zornitza Stark Classified gene: DPH2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3372 DPH2 Zornitza Stark Gene: dph2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3371 EIF2AK2 Zornitza Stark Marked gene: EIF2AK2 as ready
Intellectual disability syndromic and non-syndromic v0.3371 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3371 FBRSL1 Zornitza Stark Marked gene: FBRSL1 as ready
Intellectual disability syndromic and non-syndromic v0.3371 FBRSL1 Zornitza Stark Gene: fbrsl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3371 CAMK2B Zornitza Stark Marked gene: CAMK2B as ready
Intellectual disability syndromic and non-syndromic v0.3371 CAMK2B Zornitza Stark Gene: camk2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3371 CAMK2B Zornitza Stark Phenotypes for gene: CAMK2B were changed from to Mental retardation, autosomal dominant 54, MIM# 617799
Intellectual disability syndromic and non-syndromic v0.3370 CAMK2B Zornitza Stark Publications for gene: CAMK2B were set to
Intellectual disability syndromic and non-syndromic v0.3369 CAMK2B Zornitza Stark Mode of inheritance for gene: CAMK2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3368 CAMK2B Zornitza Stark reviewed gene: CAMK2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100089, 29560374, 32875707; Phenotypes: Mental retardation, autosomal dominant 54, MIM# 617799; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3368 RALGAPB Elena Savva gene: RALGAPB was added
gene: RALGAPB was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RALGAPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RALGAPB were set to PMID: 32853829
Phenotypes for gene: RALGAPB were set to Neurodevelopmental disorders, autism
Review for gene: RALGAPB was set to RED
Added comment: PMID: 32853829 - Reviews previous publications and identifies 10 de novo variants (5 PTCs, 5 missense) in patients with ASD (7/10), epilepsy (2/10) and developmental delay (1/10).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3368 RNU7-1 Paul De Fazio gene: RNU7-1 was added
gene: RNU7-1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to 33230297
Phenotypes for gene: RNU7-1 were set to Aicardi–Goutières syndrome-like
Review for gene: RNU7-1 was set to GREEN
gene: RNU7-1 was marked as current diagnostic
Added comment: Review originally submitted by Ming Wong
- 16 affected individuals from 11 families
- Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of
replication-dependent histone (RDH) mRNAs
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3368 LSM11 Ee Ming Wong gene: LSM11 was added
gene: LSM11 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LSM11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM11 were set to PMID: 33230297
Phenotypes for gene: LSM11 were set to type I interferonopathy Aicardi–Goutières syndrome
Review for gene: LSM11 was set to RED
gene: LSM11 was marked as current diagnostic
Added comment: - Two affected siblings from a consanguineous family carrying a homozygous variant in LSM11
- Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of
replication-dependent histone (RDH) mRNAs
- Knockdown of LSM11 in THP-1 cells results in an increase in misprocessed RDH mRNA and
interferon signaling

(added as Red as per discussion with Seb)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3368 FBRSL1 Sue White Classified gene: FBRSL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3368 FBRSL1 Sue White Gene: fbrsl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3367 DPH2 Paul De Fazio gene: DPH2 was added
gene: DPH2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DPH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPH2 were set to 32576952; 27421267
Phenotypes for gene: DPH2 were set to Diphthamide-deficiency syndrome
Review for gene: DPH2 was set to AMBER
gene: DPH2 was marked as current diagnostic
Added comment: One 19 month old reported (PMID:32576952) with biallelic (one missense, one nonsense) variants in DPH2, with phenotype similar to DPH1 deficiency (gross motor delay, not walking, fine motor and expressive language delays, macrocephaly)

Another family (sibs) was previously reported with biallelic nonsense variants (PMID:27421267) with a comparable phenotype, this family also has biallelic variants in KALRN and the authors thought those variants more likely causative. Patients had ID and microcephaly (in contrast to the 19 month old above).

In vitro functional assays support reduced diphthamide synthesis activity for the variants identified in PMID:32576952.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3367 EIF2AK2 Seb Lunke reviewed gene: EIF2AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.3367 FBRSL1 Elena Savva gene: FBRSL1 was added
gene: FBRSL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FBRSL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FBRSL1 were set to PMID: 32424618
Phenotypes for gene: FBRSL1 were set to Malformation and intellectual disability syndrome
Review for gene: FBRSL1 was set to GREEN
Added comment: Three children with de novo PTCs that escape NMD, and an overlapping syndromic phenotype with respiratory insufficiency, postnatal growth restriction, microcephaly, global developmental delay and other malformations. 2/3 had heart defects, cleft palate and hearing impairement.
Supported by Xenopus oocyte functional studies
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3367 MLYCD Zornitza Stark Marked gene: MLYCD as ready
Intellectual disability syndromic and non-syndromic v0.3367 MLYCD Zornitza Stark Gene: mlycd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3367 MLYCD Zornitza Stark Phenotypes for gene: MLYCD were changed from to Malonyl-CoA decarboxylase deficiency, MIM# 248360
Intellectual disability syndromic and non-syndromic v0.3366 MLYCD Zornitza Stark Publications for gene: MLYCD were set to
Intellectual disability syndromic and non-syndromic v0.3365 MLYCD Zornitza Stark Mode of inheritance for gene: MLYCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3364 MLYCD Zornitza Stark reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 12955715; Phenotypes: Malonyl-CoA decarboxylase deficiency, MIM# 248360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3364 KCNQ3 Zornitza Stark Marked gene: KCNQ3 as ready
Intellectual disability syndromic and non-syndromic v0.3364 KCNQ3 Zornitza Stark Gene: kcnq3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3364 KCNQ3 Zornitza Stark Phenotypes for gene: KCNQ3 were changed from to Seizures, benign neonatal, 2, MIM# 121201
Intellectual disability syndromic and non-syndromic v0.3363 KCNQ3 Zornitza Stark Publications for gene: KCNQ3 were set to
Intellectual disability syndromic and non-syndromic v0.3362 KCNQ3 Zornitza Stark Mode of inheritance for gene: KCNQ3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3361 KCNQ3 Zornitza Stark reviewed gene: KCNQ3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33337327, 25524373, 24851285; Phenotypes: Seizures, benign neonatal, 2, MIM# 121201; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3361 PRKACB Zornitza Stark Phenotypes for gene: PRKACB were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, MIM# 619143; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.3360 PRKACB Zornitza Stark reviewed gene: PRKACB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardioacrofacial dysplasia 2, MIM# 619143; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3360 YIF1B Zornitza Stark Phenotypes for gene: YIF1B were changed from Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement to Kaya-Barakat-Masson syndrome, MIM# 619125; Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Intellectual disability syndromic and non-syndromic v0.3359 YIF1B Zornitza Stark reviewed gene: YIF1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kaya-Barakat-Masson syndrome, MIM# 619125, Central hypotonia, Failure to thrive, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Spasticity, Abnormality of movement; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3359 ATIC Zornitza Stark Marked gene: ATIC as ready
Intellectual disability syndromic and non-syndromic v0.3359 ATIC Zornitza Stark Gene: atic has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3359 ATIC Zornitza Stark Phenotypes for gene: ATIC were changed from to AICA-ribosiduria due to ATIC deficiency, MIM# 608688
Intellectual disability syndromic and non-syndromic v0.3358 ATIC Zornitza Stark Publications for gene: ATIC were set to
Intellectual disability syndromic and non-syndromic v0.3357 ATIC Zornitza Stark Mode of inheritance for gene: ATIC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3356 ATIC Zornitza Stark reviewed gene: ATIC: Rating: GREEN; Mode of pathogenicity: None; Publications: 15114530, 32557644; Phenotypes: AICA-ribosiduria due to ATIC deficiency, MIM# 608688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3356 SOX2 Zornitza Stark Phenotypes for gene: SOX2 were changed from Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900 to Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900
Intellectual disability syndromic and non-syndromic v0.3356 SOX2 Zornitza Stark Phenotypes for gene: SOX2 were changed from to Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900
Intellectual disability syndromic and non-syndromic v0.3355 SOX2 Zornitza Stark Publications for gene: SOX2 were set to
Intellectual disability syndromic and non-syndromic v0.3354 SOX2 Zornitza Stark Mode of inheritance for gene: SOX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3353 SOX2 Zornitza Stark reviewed gene: SOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30450772, 28121235, 25542770, 24498598, 24211324, 24033328, 21326281; Phenotypes: Microphthalmia, syndromic 3, MIM# 206900, Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3353 RERE Zornitza Stark Marked gene: RERE as ready
Intellectual disability syndromic and non-syndromic v0.3353 RERE Zornitza Stark Gene: rere has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3353 RERE Zornitza Stark Phenotypes for gene: RERE were changed from to Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, MIM# 616975
Intellectual disability syndromic and non-syndromic v0.3352 RERE Zornitza Stark Publications for gene: RERE were set to
Intellectual disability syndromic and non-syndromic v0.3351 RERE Zornitza Stark Mode of inheritance for gene: RERE was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3350 RERE Zornitza Stark reviewed gene: RERE: Rating: GREEN; Mode of pathogenicity: None; Publications: 27087320, 23451234, 30896913, 30061196; Phenotypes: Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, MIM# 616975; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3350 RARB Zornitza Stark Marked gene: RARB as ready
Intellectual disability syndromic and non-syndromic v0.3350 RARB Zornitza Stark Gene: rarb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3350 RARB Zornitza Stark Phenotypes for gene: RARB were changed from to Microphthalmia, syndromic 12, MIM# 615524
Intellectual disability syndromic and non-syndromic v0.3349 RARB Zornitza Stark Publications for gene: RARB were set to
Intellectual disability syndromic and non-syndromic v0.3348 RARB Zornitza Stark Mode of inheritance for gene: RARB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3347 RARB Zornitza Stark reviewed gene: RARB: Rating: GREEN; Mode of pathogenicity: None; Publications: 30880327, 30281527, 24075189, 27120018, 25457163, 17506106; Phenotypes: Microphthalmia, syndromic 12, MIM# 615524; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3347 SMOC1 Zornitza Stark Marked gene: SMOC1 as ready
Intellectual disability syndromic and non-syndromic v0.3347 SMOC1 Zornitza Stark Gene: smoc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3347 SMOC1 Zornitza Stark Phenotypes for gene: SMOC1 were changed from to Microphthalmia with limb anomalies, MIM# 206920
Intellectual disability syndromic and non-syndromic v0.3346 SMOC1 Zornitza Stark Publications for gene: SMOC1 were set to
Intellectual disability syndromic and non-syndromic v0.3345 SMOC1 Zornitza Stark Mode of inheritance for gene: SMOC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3344 SMOC1 Zornitza Stark reviewed gene: SMOC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21194678, 21194680, 30445150; Phenotypes: Microphthalmia with limb anomalies, MIM# 206920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3344 MAB21L2 Zornitza Stark Marked gene: MAB21L2 as ready
Intellectual disability syndromic and non-syndromic v0.3344 MAB21L2 Zornitza Stark Gene: mab21l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3344 MAB21L2 Zornitza Stark Phenotypes for gene: MAB21L2 were changed from to Microphthalmia/coloboma and skeletal dysplasia syndrome, MIM# 615877
Intellectual disability syndromic and non-syndromic v0.3343 MAB21L2 Zornitza Stark Publications for gene: MAB21L2 were set to
Intellectual disability syndromic and non-syndromic v0.3342 MAB21L2 Zornitza Stark Mode of inheritance for gene: MAB21L2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3341 MAB21L2 Zornitza Stark reviewed gene: MAB21L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24906020, 25719200, 31037784, 30375740, 30073347, 26116559; Phenotypes: Microphthalmia/coloboma and skeletal dysplasia syndrome, MIM# 615877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3341 PDSS1 Zornitza Stark Marked gene: PDSS1 as ready
Intellectual disability syndromic and non-syndromic v0.3341 PDSS1 Zornitza Stark Gene: pdss1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3341 PDSS1 Zornitza Stark Phenotypes for gene: PDSS1 were changed from to Coenzyme Q10 deficiency, primary, 2 MIM#614651
Intellectual disability syndromic and non-syndromic v0.3340 PDSS1 Zornitza Stark Publications for gene: PDSS1 were set to
Intellectual disability syndromic and non-syndromic v0.3339 PDSS1 Zornitza Stark Mode of inheritance for gene: PDSS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3338 PDSS1 Paul De Fazio reviewed gene: PDSS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17332895, 22494076, 33285023; Phenotypes: Coenzyme Q10 deficiency, primary, 2 MIM#614651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.3338 C16orf62 Zornitza Stark Phenotypes for gene: C16orf62 were changed from 3C/Ritscher-Schinzel-like syndrome to Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135
Intellectual disability syndromic and non-syndromic v0.3337 C16orf62 Zornitza Stark edited their review of gene: C16orf62: Changed phenotypes: Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135
Intellectual disability syndromic and non-syndromic v0.3337 GAD1 Zornitza Stark Phenotypes for gene: GAD1 were changed from Cerebral palsy, spastic quadriplegic, 1, MIM#603513; Developmental and epileptic encephalopathy to Cerebral palsy, spastic quadriplegic, 1, MIM#603513; Developmental and epileptic encephalopathy 89, MIM# 619124
Intellectual disability syndromic and non-syndromic v0.3336 GAD1 Zornitza Stark edited their review of gene: GAD1: Changed phenotypes: Cerebral palsy, spastic quadriplegic, 1, MIM#603513, Developmental and epileptic encephalopathy 89, MIM# 619124
Intellectual disability syndromic and non-syndromic v0.3336 XYLT1 Zornitza Stark Phenotypes for gene: XYLT1 were changed from Desbuquois dysplasia 2; OMIM# 615777 to Desbuquois dysplasia 2, MIM# 615777; Baratela-Scott syndrome
Intellectual disability syndromic and non-syndromic v0.3335 XYLT1 Zornitza Stark Tag SV/CNV tag was added to gene: XYLT1.
Tag STR tag was added to gene: XYLT1.
Intellectual disability syndromic and non-syndromic v0.3335 XYLT1 Zornitza Stark reviewed gene: XYLT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30554721, 24581741, 23982343; Phenotypes: Desbuquois dysplasia 2, MIM# 615777, Baratela-Scott syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3335 TUSC3 Zornitza Stark Tag SV/CNV tag was added to gene: TUSC3.
Intellectual disability syndromic and non-syndromic v0.3335 TUSC3 Zornitza Stark Marked gene: TUSC3 as ready
Intellectual disability syndromic and non-syndromic v0.3335 TUSC3 Zornitza Stark Gene: tusc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3335 TUSC3 Zornitza Stark Phenotypes for gene: TUSC3 were changed from to Mental retardation, autosomal recessive 7, MIM# 611093, MONDO:0012615; TUSC3-CDG (Disorders of protein N-glycosylation)
Intellectual disability syndromic and non-syndromic v0.3334 TUSC3 Zornitza Stark Publications for gene: TUSC3 were set to
Intellectual disability syndromic and non-syndromic v0.3333 TUSC3 Zornitza Stark Mode of inheritance for gene: TUSC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3332 TUSC3 Zornitza Stark reviewed gene: TUSC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18452889, 18455129, 21739581, 27148795, 31606977; Phenotypes: Mental retardation, autosomal recessive 7, MIM# 611093, MONDO:0012615, TUSC3-CDG (Disorders of protein N-glycosylation); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3332 TMEM165 Zornitza Stark Marked gene: TMEM165 as ready
Intellectual disability syndromic and non-syndromic v0.3332 TMEM165 Zornitza Stark Gene: tmem165 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3332 TMEM165 Zornitza Stark Phenotypes for gene: TMEM165 were changed from to Congenital disorder of glycosylation, type IIk, MIM# 614727; TMEM165-CDG, MONDO:0013870
Intellectual disability syndromic and non-syndromic v0.3331 TMEM165 Zornitza Stark Publications for gene: TMEM165 were set to
Intellectual disability syndromic and non-syndromic v0.3330 TMEM165 Zornitza Stark Mode of inheritance for gene: TMEM165 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3329 TMEM165 Zornitza Stark reviewed gene: TMEM165: Rating: GREEN; Mode of pathogenicity: None; Publications: 22683087, 28323990, 27401145, 27008884, 26238249, 25609749; Phenotypes: Congenital disorder of glycosylation, type IIk, MIM# 614727, TMEM165-CDG, MONDO:0013870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3329 EXT2 Zornitza Stark Publications for gene: EXT2 were set to
Intellectual disability syndromic and non-syndromic v0.3328 EXT2 Zornitza Stark edited their review of gene: EXT2: Changed publications: 30288735, 30075207, 26246518
Intellectual disability syndromic and non-syndromic v0.3328 ST3GAL5 Zornitza Stark Phenotypes for gene: ST3GAL5 were changed from Salt and pepper developmental regression syndrome; OMIM #609056 to Salt and pepper developmental regression syndrome 609056; GM3 synthase deficiency, MONDO:0018274; Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation)
Intellectual disability syndromic and non-syndromic v0.3327 ST3GAL5 Zornitza Stark Publications for gene: ST3GAL5 were set to PubMed: 15502825; 22990144; 24026681; 27232954; 30185102; 24026681
Intellectual disability syndromic and non-syndromic v0.3326 ST3GAL5 Zornitza Stark Tag founder tag was added to gene: ST3GAL5.
Intellectual disability syndromic and non-syndromic v0.3326 ST3GAL5 Zornitza Stark reviewed gene: ST3GAL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23436467, 22990144, 15502825, 27232954, 30691927, 30688114, 30576498; Phenotypes: Salt and pepper developmental regression syndrome 609056, GM3 synthase deficiency, MONDO:0018274, Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3326 DPYD Ain Roesley reviewed gene: DPYD: Rating: AMBER; Mode of pathogenicity: None; Publications: 10071185, 25565930, 30349988, 28275972, 17065071, 21114665, 22003227, 28123791; Phenotypes: Dihydropyrimidine dehydrogenase deficiency (MIM#274270); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3326 RFT1 Zornitza Stark Marked gene: RFT1 as ready
Intellectual disability syndromic and non-syndromic v0.3326 RFT1 Zornitza Stark Gene: rft1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3326 RFT1 Zornitza Stark Phenotypes for gene: RFT1 were changed from to Congenital disorder of glycosylation, type In, MIM# 612015; RFT1-CDG, MONDO:0012783
Intellectual disability syndromic and non-syndromic v0.3325 RFT1 Zornitza Stark Publications for gene: RFT1 were set to
Intellectual disability syndromic and non-syndromic v0.3324 RFT1 Zornitza Stark Mode of inheritance for gene: RFT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3323 RFT1 Zornitza Stark reviewed gene: RFT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18313027, 19701946, 19856127, 23111317, 30071302, 29923091, 27927990, 26892341; Phenotypes: Congenital disorder of glycosylation, type In, MIM# 612015, RFT1-CDG, MONDO:0012783; Mode of inheritance: BIALLELIC, 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 v0.3320 MPI Zornitza Stark Marked gene: MPI as ready
Intellectual disability syndromic and non-syndromic v0.3320 MPI Zornitza Stark Gene: mpi has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3320 MPI Zornitza Stark Phenotypes for gene: MPI were changed from to Congenital disorder of glycosylation, type Ib, MIM# 602579; MPI-CDG MONDO:0011257
Intellectual disability syndromic and non-syndromic v0.3319 MPI Zornitza Stark Publications for gene: MPI were set to
Intellectual disability syndromic and non-syndromic v0.3318 MPI Zornitza Stark Mode of inheritance for gene: MPI was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3317 MPI Zornitza Stark Classified gene: MPI as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3317 MPI Zornitza Stark Gene: mpi has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3316 MPI Zornitza Stark reviewed gene: MPI: Rating: RED; Mode of pathogenicity: None; Publications: 12414827, 9585601, 10980531, 33098580, 33204592, 32905087, 32266963, 30242110; Phenotypes: Congenital disorder of glycosylation, type Ib, MIM# 602579, MPI-CDG MONDO:0011257; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3316 PGM3 Zornitza Stark Marked gene: PGM3 as ready
Intellectual disability syndromic and non-syndromic v0.3316 PGM3 Zornitza Stark Gene: pgm3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3316 PGM3 Zornitza Stark Phenotypes for gene: PGM3 were changed from to Immunodeficiency 23, MIM# 615816; PGM3-CDG, MONDO:0014353
Intellectual disability syndromic and non-syndromic v0.3315 PGM3 Zornitza Stark Publications for gene: PGM3 were set to
Intellectual disability syndromic and non-syndromic v0.3314 PGM3 Zornitza Stark Mode of inheritance for gene: PGM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3313 PGM3 Zornitza Stark reviewed gene: PGM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30578875, 31231132, 33098103, 30157810, 28704707; Phenotypes: Immunodeficiency 23, MIM# 615816, PGM3-CDG, MONDO:0014353; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3313 PGAP3 Zornitza Stark Marked gene: PGAP3 as ready
Intellectual disability syndromic and non-syndromic v0.3313 PGAP3 Zornitza Stark Gene: pgap3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3313 PGAP3 Zornitza Stark Phenotypes for gene: PGAP3 were changed from to Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318
Intellectual disability syndromic and non-syndromic v0.3312 PGAP3 Zornitza Stark Publications for gene: PGAP3 were set to 24439110; 29620724; 30345601; 30217754
Intellectual disability syndromic and non-syndromic v0.3311 PGAP3 Zornitza Stark Publications for gene: PGAP3 were set to
Intellectual disability syndromic and non-syndromic v0.3310 PGAP3 Zornitza Stark Mode of inheritance for gene: PGAP3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3309 PGAP3 Zornitza Stark reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24439110, 29620724, 30345601, 30217754; Phenotypes: Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3309 PGAP2 Zornitza Stark Marked gene: PGAP2 as ready
Intellectual disability syndromic and non-syndromic v0.3309 PGAP2 Zornitza Stark Gene: pgap2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3309 PGAP2 Zornitza Stark Phenotypes for gene: PGAP2 were changed from to Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628
Intellectual disability syndromic and non-syndromic v0.3308 PGAP2 Zornitza Stark Publications for gene: PGAP2 were set to
Intellectual disability syndromic and non-syndromic v0.3307 PGAP2 Zornitza Stark Mode of inheritance for gene: PGAP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3306 PGAP2 Zornitza Stark reviewed gene: PGAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561846, 23561847, 31805394, 29119105, 27871432; Phenotypes: Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3306 PIGV Zornitza Stark Marked gene: PIGV as ready
Intellectual disability syndromic and non-syndromic v0.3306 PIGV Zornitza Stark Gene: pigv has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3306 PIGV Zornitza Stark Phenotypes for gene: PIGV were changed from to Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398
Intellectual disability syndromic and non-syndromic v0.3305 PIGV Zornitza Stark Publications for gene: PIGV were set to
Intellectual disability syndromic and non-syndromic v0.3304 PIGV Zornitza Stark Mode of inheritance for gene: PIGV was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3303 PIGV Zornitza Stark reviewed gene: PIGV: Rating: GREEN; Mode of pathogenicity: None; Publications: 20802478, 22315194, 28817240, 24129430; Phenotypes: Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3303 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398 to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398, MONDO:0014165
Intellectual disability syndromic and non-syndromic v0.3302 PIGT Zornitza Stark edited their review of gene: PIGT: Changed phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398, MONDO:0014165
Intellectual disability syndromic and non-syndromic v0.3302 PIGO Zornitza Stark Marked gene: PIGO as ready
Intellectual disability syndromic and non-syndromic v0.3302 PIGO Zornitza Stark Gene: pigo has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3302 PIGO Zornitza Stark Phenotypes for gene: PIGO were changed from to Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882
Intellectual disability syndromic and non-syndromic v0.3301 PIGO Zornitza Stark Publications for gene: PIGO were set to
Intellectual disability syndromic and non-syndromic v0.3300 PIGO Zornitza Stark Mode of inheritance for gene: PIGO was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3299 PIGO Zornitza Stark reviewed gene: PIGO: Rating: GREEN; Mode of pathogenicity: None; Publications: 22683086, 31698102, 28900819, 28545593, 28337824; Phenotypes: Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3299 PIGN Zornitza Stark Marked gene: PIGN as ready
Intellectual disability syndromic and non-syndromic v0.3299 PIGN Zornitza Stark Gene: pign has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3299 PIGN Zornitza Stark Phenotypes for gene: PIGN were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563
Intellectual disability syndromic and non-syndromic v0.3298 PIGN Zornitza Stark Publications for gene: PIGN were set to
Intellectual disability syndromic and non-syndromic v0.3297 PIGN Zornitza Stark Mode of inheritance for gene: PIGN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3296 PIGN Zornitza Stark reviewed gene: PIGN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21493957, 24253414, 26364997, 26394714, 33193741, 32585529, 29330547; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 1, MIM# 614080, MONDO:0013563; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3296 PIGL Zornitza Stark Marked gene: PIGL as ready
Intellectual disability syndromic and non-syndromic v0.3296 PIGL Zornitza Stark Gene: pigl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3296 PIGL Zornitza Stark Phenotypes for gene: PIGL were changed from to CHIME syndrome, MIM# 280000, MONDO:0010221
Intellectual disability syndromic and non-syndromic v0.3295 PIGL Zornitza Stark Publications for gene: PIGL were set to
Intellectual disability syndromic and non-syndromic v0.3294 PIGL Zornitza Stark Tag SV/CNV tag was added to gene: PIGL.
Tag founder tag was added to gene: PIGL.
Intellectual disability syndromic and non-syndromic v0.3294 PIGL Zornitza Stark Mode of inheritance for gene: PIGL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3293 PIGL Zornitza Stark reviewed gene: PIGL: Rating: GREEN; Mode of pathogenicity: None; Publications: 22444671, 31535386, 30023290, 29473937, 28371479, 25706356; Phenotypes: CHIME syndrome, MIM# 280000, MONDO:0010221; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3293 B3GALNT2 Zornitza Stark Marked gene: B3GALNT2 as ready
Intellectual disability syndromic and non-syndromic v0.3293 B3GALNT2 Zornitza Stark Gene: b3galnt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3293 B3GALNT2 Zornitza Stark Phenotypes for gene: B3GALNT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, MIM# 615181; MONDO:0014071
Intellectual disability syndromic and non-syndromic v0.3292 B3GALNT2 Zornitza Stark Publications for gene: B3GALNT2 were set to
Intellectual disability syndromic and non-syndromic v0.3291 B3GALNT2 Zornitza Stark Mode of inheritance for gene: B3GALNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3290 B3GALNT2 Zornitza Stark reviewed gene: B3GALNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23453667, 33290285, 29791932, 29273094, 28688748, 28303321; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, MIM# 615181, MONDO:0014071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3290 MPDU1 Zornitza Stark Marked gene: MPDU1 as ready
Intellectual disability syndromic and non-syndromic v0.3290 MPDU1 Zornitza Stark Gene: mpdu1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3290 MPDU1 Zornitza Stark Phenotypes for gene: MPDU1 were changed from to Congenital disorder of glycosylation, type If, MIM# 609180; MPDU1-CDG, MONDO:0012211
Intellectual disability syndromic and non-syndromic v0.3289 MPDU1 Zornitza Stark Publications for gene: MPDU1 were set to
Intellectual disability syndromic and non-syndromic v0.3288 MPDU1 Zornitza Stark Mode of inheritance for gene: MPDU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3287 MPDU1 Zornitza Stark reviewed gene: MPDU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11733564, 11733556, 31741824, 29721919; Phenotypes: Congenital disorder of glycosylation, type If, MIM# 609180, MPDU1-CDG, MONDO:0012211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3287 DPAGT1 Zornitza Stark Marked gene: DPAGT1 as ready
Intellectual disability syndromic and non-syndromic v0.3287 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3287 DPAGT1 Zornitza Stark Phenotypes for gene: DPAGT1 were changed from to Congenital disorder of glycosylation, type Ij, MIM# 608093; DPAGT1-CDG MONDO:0011964
Intellectual disability syndromic and non-syndromic v0.3286 DPAGT1 Zornitza Stark Publications for gene: DPAGT1 were set to
Intellectual disability syndromic and non-syndromic v0.3285 DPAGT1 Zornitza Stark Mode of inheritance for gene: DPAGT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3284 DPAGT1 Zornitza Stark reviewed gene: DPAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12872255, 22492991, 22304930, 31153949, 30653653, 30117111; Phenotypes: Congenital disorder of glycosylation, type Ij, MIM# 608093, DPAGT1-CDG MONDO:0011964; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3284 DOLK Zornitza Stark Marked gene: DOLK as ready
Intellectual disability syndromic and non-syndromic v0.3284 DOLK Zornitza Stark Gene: dolk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3284 DOLK Zornitza Stark Phenotypes for gene: DOLK were changed from to DK1-CDG, MONDO:0012556; Congenital disorder of glycosylation, type Im, MIM# 610768
Intellectual disability syndromic and non-syndromic v0.3283 DOLK Zornitza Stark Publications for gene: DOLK were set to
Intellectual disability syndromic and non-syndromic v0.3282 DOLK Zornitza Stark Mode of inheritance for gene: DOLK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3281 DOLK Zornitza Stark reviewed gene: DOLK: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273964, 22242004, 23890587, 30653653, 28816422, 24144945; Phenotypes: DK1-CDG, MONDO:0012556, Congenital disorder of glycosylation, type Im, MIM# 610768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3281 DPYD Elena Savva Deleted their review
Intellectual disability syndromic and non-syndromic v0.3281 EZH2 Zornitza Stark Marked gene: EZH2 as ready
Intellectual disability syndromic and non-syndromic v0.3281 EZH2 Zornitza Stark Gene: ezh2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3281 EZH2 Zornitza Stark Phenotypes for gene: EZH2 were changed from to Weaver syndrome MIM#277590
Intellectual disability syndromic and non-syndromic v0.3280 EZH2 Zornitza Stark Publications for gene: EZH2 were set to
Intellectual disability syndromic and non-syndromic v0.3279 EZH2 Zornitza Stark Mode of inheritance for gene: EZH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3278 EZH2 Zornitza Stark reviewed gene: EZH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29244146, 23865096; Phenotypes: Weaver syndrome MIM#277590; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3278 DPYD Elena Savva reviewed gene: DPYD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29152729; Phenotypes: 5-fluorouracil toxicity MIM#274270, Dihydropyrimidine dehydrogenase deficiency MIM#274270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3278 COG5 Zornitza Stark Marked gene: COG5 as ready
Intellectual disability syndromic and non-syndromic v0.3278 COG5 Zornitza Stark Gene: cog5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3278 COG5 Zornitza Stark Phenotypes for gene: COG5 were changed from to Congenital disorder of glycosylation, type IIi, MIM# 613612
Intellectual disability syndromic and non-syndromic v0.3277 COG5 Zornitza Stark Publications for gene: COG5 were set to
Intellectual disability syndromic and non-syndromic v0.3276 COG5 Zornitza Stark Mode of inheritance for gene: COG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3275 COG5 Zornitza Stark reviewed gene: COG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23228021, 31572517, 32174980; Phenotypes: Congenital disorder of glycosylation, type IIi, MIM# 613612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3275 SHMT2 Zornitza Stark Phenotypes for gene: SHMT2 were changed from Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly to Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB), MIM#619121; Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Intellectual disability syndromic and non-syndromic v0.3274 SHMT2 Zornitza Stark reviewed gene: SHMT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB), MIM#619121, Congenital microcephaly, Infantile axial hypotonia, Spastic paraparesis, Global developmental delay, Intellectual disability, Abnormality of the corpus callosum, Abnormal cortical gyration, Hypertrophic cardiomyopathy, Abnormality of the face, Proximal placement of thumb, 2-3 toe syndactylyCongenital microcephaly, Infantile axial hypotonia, Spastic paraparesis, Global developmental delay, Intellectual disability, Abnormality of the corpus callosum, Abnormal cortical gyration, Hypertrophic cardiomyopathy, Abnormality of the face, Proximal placement of thumb, 2-3 toe syndactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3274 PPIL1 Zornitza Stark Marked gene: PPIL1 as ready
Intellectual disability syndromic and non-syndromic v0.3274 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3274 PPIL1 Zornitza Stark Classified gene: PPIL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3274 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3273 PPIL1 Zornitza Stark gene: PPIL1 was added
gene: PPIL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIL1 were set to 33220177
Phenotypes for gene: PPIL1 were set to Pontocerebellar hypoplasia; microcephaly; seizures
Review for gene: PPIL1 was set to GREEN
Added comment: 17 individuals from 9 unrelated families reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID. Mouse models support gene-disease association.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3272 DIP2B Bryony Thompson Classified gene: DIP2B as No list
Intellectual disability syndromic and non-syndromic v0.3272 DIP2B Bryony Thompson Added comment: Comment on list classification: Only repeat expansion reported. Added as an STR
Intellectual disability syndromic and non-syndromic v0.3272 DIP2B Bryony Thompson Gene: dip2b has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.3271 FRA12A Bryony Thompson Marked STR: FRA12A as ready
Intellectual disability syndromic and non-syndromic v0.3271 FRA12A Bryony Thompson Str: fra12a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3271 FRA12A Bryony Thompson Classified STR: FRA12A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3271 FRA12A Bryony Thompson Str: fra12a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3270 FRA12A Bryony Thompson STR: FRA12A was added
STR: FRA12A was added to Intellectual disability syndromic and non-syndromic. Sources: Other
5'UTR tags were added to STR: FRA12A.
Mode of inheritance for STR: FRA12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FRA12A were set to 17236128
Phenotypes for STR: FRA12A were set to Mental retardation, FRA12A type MIM#136630
Review for STR: FRA12A was set to AMBER
Added comment: NM_173602.2:c.-137CGG[X]
All individuals expressing FRA12A had CGG-repeat expansion. The length of the expanded allele in 3 unaffected FRA12A carriers was 650–850 bp. In the two affected patients from 2 families with FRA12A, the length of the expanded allele was ∼1,050-1,150 bp.
70 controls used to determine the "normal" repeat range.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.3269 FRAXE Bryony Thompson Classified STR: FRAXE as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3269 FRAXE Bryony Thompson Str: fraxe has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3268 FRAXE Bryony Thompson STR: FRAXE was added
STR: FRAXE was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for STR: FRAXE was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: FRAXE were set to 8334699; 8673085; 11388762
Phenotypes for STR: FRAXE were set to Fragile X syndrome, FRAXE type (OMIM 309548)
Review for STR: FRAXE was set to GREEN
STR: FRAXE was marked as clinically relevant
STR: FRAXE was marked as current diagnostic
Added comment: NM_001169122.1(AFF2):c.-460_-458GCC(6_25)
Loss of function through methylation silencing is the mechanism of disease
Normal - 5-44 repeats
Inconclusive - 45-54 repeats
Premutation - 55-200 repeats
Abnormal - >200 or >230 repeats
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3267 RAP1B Zornitza Stark Publications for gene: RAP1B were set to PMID: 32627184
Intellectual disability syndromic and non-syndromic v0.3266 RAP1B Zornitza Stark Classified gene: RAP1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3266 RAP1B Zornitza Stark Gene: rap1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3265 RAP1B Zornitza Stark edited their review of gene: RAP1B: Added comment: Another individual with de novo missense variant from a Kabuki-like cohort but note facial gestalt was not typical, had DD.; Changed rating: GREEN; Changed publications: 32627184, 26280580
Intellectual disability syndromic and non-syndromic v0.3265 RAP1B Zornitza Stark reviewed gene: RAP1B: Rating: AMBER; Mode of pathogenicity: None; Publications: 32627184; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3265 RAP1B Zornitza Stark Marked gene: RAP1B as ready
Intellectual disability syndromic and non-syndromic v0.3265 RAP1B Zornitza Stark Gene: rap1b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3265 RAP1B Zornitza Stark Classified gene: RAP1B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3265 RAP1B Zornitza Stark Gene: rap1b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3264 RAP1B Chirag Patel gene: RAP1B was added
gene: RAP1B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAP1B were set to PMID: 32627184
Phenotypes for gene: RAP1B were set to RAP1B‐associated phenotype, no OMIM #
Review for gene: RAP1B was set to RED
Added comment: De novo variants in the RAP1B gene (c.35G>T p.(Gly12Val) and c.178G>C p.(Gly60Arg)) in two unrelated patients with thrombocytopenia, microcephaly, learning difficulties, renal malformations, structural anomalies of the brain and other features (not Kabuki like).

RAP1B is a member of the RAS superfamily of small GTPases. There is strong evidence that the p.Gly12Val and p.Gly60Arg variants in the RAP1B gene lead into a dysregulation of the downstream pathway. Both substitutions have been described previously as dominant constitutively active in RAS‐related proteins (gain of function variants).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3263 EMC10 Chirag Patel gene: EMC10 was added
gene: EMC10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EMC10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMC10 were set to PMID: 32869858
Phenotypes for gene: EMC10 were set to Developmental delay and intellectual disability, no OMIM#
Review for gene: EMC10 was set to RED
Added comment: Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders.

One Saudi family with 2 affected individuals with mild ID, speech delay, and GDD.
WES and Sanger sequencing revealed a homozygous splice acceptor site variant (c.679‐1G>A) in EMC10 . Variant segregated within the family. RT‐qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3262 FBXO28 Zornitza Stark changed review comment from: Nine new individuals with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and all 10 known cases reviewed to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features.
Sources: Literature; to: Nine new individuals with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and all 10 known cases reviewed to delineate the phenotypic spectrum. All had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3262 FBXO28 Zornitza Stark Marked gene: FBXO28 as ready
Intellectual disability syndromic and non-syndromic v0.3262 FBXO28 Zornitza Stark Gene: fbxo28 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3262 FBXO28 Zornitza Stark Classified gene: FBXO28 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3262 FBXO28 Zornitza Stark Gene: fbxo28 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3261 FBXO28 Zornitza Stark gene: FBXO28 was added
gene: FBXO28 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FBXO28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXO28 were set to 33280099
Phenotypes for gene: FBXO28 were set to Developmental and epileptic encephalopathy
Review for gene: FBXO28 was set to GREEN
Added comment: Nine new individuals with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and all 10 known cases reviewed to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3260 RLIM Zornitza Stark Publications for gene: RLIM were set to 29728705; 25735484; 25644381
Intellectual disability syndromic and non-syndromic v0.3259 RLIM Zornitza Stark Mode of pathogenicity for gene: RLIM was changed from to Other
Intellectual disability syndromic and non-syndromic v0.3258 RLIM Zornitza Stark changed review comment from: 14 males from 9 families reported with duplications involving RLIM gene, suggesting dosage effect.; to: 14 males from 9 families reported with duplications involving RLIM gene and intellectual disability, suggesting dosage effect.
Intellectual disability syndromic and non-syndromic v0.3258 RLIM Zornitza Stark edited their review of gene: RLIM: Added comment: 14 males from 9 families reported with duplications involving RLIM gene, suggesting dosage effect.; Changed mode of pathogenicity: Other; Changed publications: 29728705, 25735484, 25644381, 33159883
Intellectual disability syndromic and non-syndromic v0.3258 CLCN6 Zornitza Stark Marked gene: CLCN6 as ready
Intellectual disability syndromic and non-syndromic v0.3258 CLCN6 Zornitza Stark Gene: clcn6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3258 CLCN6 Zornitza Stark Classified gene: CLCN6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3258 CLCN6 Zornitza Stark Gene: clcn6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3257 CLCN6 Zornitza Stark gene: CLCN6 was added
gene: CLCN6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CLCN6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLCN6 were set to 33217309
Phenotypes for gene: CLCN6 were set to Developmental delay; neurodegeneration
Review for gene: CLCN6 was set to GREEN
Added comment: Three unrelated families reported with recurrent GOF de novo c.1658A>G (p.Tyr553Cys) and severe developmental delay with pronounced generalized hypotonia, respiratory insufficiency, and variable neurodegeneration and diffusion restriction in cerebral peduncles, midbrain, and/or brainstem in MRI scans.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3256 HS2ST1 Zornitza Stark Phenotypes for gene: HS2ST1 were changed from to Intellectual disability; dysmorphic features; congenital anomalies
Intellectual disability syndromic and non-syndromic v0.3255 KDM4B Zornitza Stark Marked gene: KDM4B as ready
Intellectual disability syndromic and non-syndromic v0.3255 KDM4B Zornitza Stark Gene: kdm4b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3255 KDM4B Zornitza Stark Classified gene: KDM4B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3255 KDM4B Zornitza Stark Gene: kdm4b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3254 SMG8 Zornitza Stark Publications for gene: SMG8 were set to 31130284
Intellectual disability syndromic and non-syndromic v0.3253 SMG8 Zornitza Stark Classified gene: SMG8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3253 SMG8 Zornitza Stark Gene: smg8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3252 HS2ST1 Elena Savva Mode of pathogenicity for gene: HS2ST1 was changed from None to None
Intellectual disability syndromic and non-syndromic v0.3252 HS2ST1 Elena Savva Classified gene: HS2ST1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3252 HS2ST1 Elena Savva Gene: hs2st1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3251 HS2ST1 Elena Savva Marked gene: HS2ST1 as ready
Intellectual disability syndromic and non-syndromic v0.3251 HS2ST1 Elena Savva Added comment: Comment when marking as ready: - 4 affected from 3 unrelated families - 3 unique missense and 2 PTCs - Developmental Delay, Corpus Callosum Hypoplasia or Aplasia, and Skeletal and Renal Abnormalities
Intellectual disability syndromic and non-syndromic v0.3251 HS2ST1 Elena Savva Gene: hs2st1 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.3251 VPS4A Elena Savva changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Intellectual disability syndromic and non-syndromic v0.3251 VPS4A Elena Savva Added comment: Comment on mode of pathogenicity: Dominant negative
Intellectual disability syndromic and non-syndromic v0.3251 VPS4A Elena Savva Mode of pathogenicity for gene: VPS4A was changed from None to Other
Intellectual disability syndromic and non-syndromic v0.3251 VPS4A Elena Savva Marked gene: VPS4A as ready
Intellectual disability syndromic and non-syndromic v0.3251 VPS4A Elena Savva Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Intellectual disability syndromic and non-syndromic v0.3251 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3251 VPS4A Elena Savva Classified gene: VPS4A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3251 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3250 VPS4A Kristin Rigbye gene: VPS4A was added
gene: VPS4A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to 33186543; 33186545
Phenotypes for gene: VPS4A were set to Neurodevelopmental disorder
Review for gene: VPS4A was set to GREEN
Added comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.

"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3249 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3249 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3250 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3249 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3249 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3249 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3249 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3249 HS2ST1 Ain Roesley gene: HS2ST1 was added
gene: HS2ST1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HS2ST1 were set to 33159882
Penetrance for gene: HS2ST1 were set to unknown
Added comment: - 4 affected from 3 unrelated families
- 3 unique missense and 2 PTCs
- Developmental Delay, Corpus Callosum Hypoplasia or Aplasia, and Skeletal and Renal Abnormalities
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3249 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3249 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3248 BICRA Elena Savva Marked gene: BICRA as ready
Intellectual disability syndromic and non-syndromic v0.3248 BICRA Elena Savva Added comment: Comment when marking as ready: 12 individuals reported, 11 de novo (1 not resolved), "with neurodevelopmental phenotypes—developmental delay (HP:0001263), intellectual disability (HP:0001249), autism spectrum disorder (HP:0000729), and/or behavioral phenotypes (HP:0000708)—and variable structural birth defects and dysmorphic features". Mostly LoF or gene deletions, but 2 missense reported. Zebrafish model supports the gene-disease association.
Intellectual disability syndromic and non-syndromic v0.3248 BICRA Elena Savva Gene: bicra has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.3248 KDM4B Kristin Rigbye gene: KDM4B was added
gene: KDM4B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KDM4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM4B were set to PMID: 33232677
Phenotypes for gene: KDM4B were set to Global developmental delay, intellectual disability and neuroanatomical defects
Review for gene: KDM4B was set to GREEN
Added comment: Nine individuals with mono-allelic de novo or inherited variants in KDM4B.

All individuals presented with dysmorphic features and global developmental delay (GDD) with language and motor skills most affected. Three individuals had a history of seizures, and four had anomalies on brain imaging ranging from agenesis of the corpus callosum with hydrocephalus to cystic formations, abnormal hippocampi, and polymicrogyria.

In a knockout mouse the total brain volume was significantly reduced with decreased
size of the hippocampal dentate gyrus, partial agenesis of the corpus callosum, and ventriculomegaly.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3248 SMG8 Kristin Rigbye reviewed gene: SMG8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33242396; Phenotypes: Neuorodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3248 BICRA Paul De Fazio gene: BICRA was added
gene: BICRA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BICRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BICRA were set to 33232675
Phenotypes for gene: BICRA were set to Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features
Review for gene: BICRA was set to GREEN
gene: BICRA was marked as current diagnostic
Added comment: 12 individuals reported, 11 de novo (1 not resolved), "with neurodevelopmental phenotypes—developmental delay (HP:0001263), intellectual disability (HP:0001249), autism spectrum disorder (HP:0000729), and/or behavioral phenotypes (HP:0000708)—and variable structural birth defects and dysmorphic features". Mostly LoF or gene deletions, but 2 missense reported. Zebrafish model supports the gene-disease association.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3248 AGO2 Zornitza Stark Classified gene: AGO2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3248 AGO2 Zornitza Stark Gene: ago2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3247 AGO2 Zornitza Stark Classified gene: AGO2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3247 AGO2 Zornitza Stark Gene: ago2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3246 AGO2 Zornitza Stark Marked gene: AGO2 as ready
Intellectual disability syndromic and non-syndromic v0.3246 AGO2 Zornitza Stark Gene: ago2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3246 AGO2 Zornitza Stark gene: AGO2 was added
gene: AGO2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AGO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGO2 were set to 33199684
Phenotypes for gene: AGO2 were set to Intellectual disability
Review for gene: AGO2 was set to GREEN
Added comment: 21 individuals reported, five variants (p.L192P, p.G201V, p.T357M, p.M364T, p.C751Y) were recurrent. Variable ID.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3245 KAT5 Zornitza Stark Deleted their comment
Intellectual disability syndromic and non-syndromic v0.3245 KAT5 Zornitza Stark Phenotypes for gene: KAT5 were changed from Severe global developmental delay; Intellectual disability; Seizures; Microcephaly; Behavioral abnormality; Sleep disturbance; Morphological abnormality of the central nervous system; Short stature; Oral cleft; Abnormality of the face to Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (NEDFASB), MIM#619103; Severe global developmental delay; Intellectual disability; Seizures; Microcephaly; Behavioral abnormality; Sleep disturbance; Morphological abnormality of the central nervous system; Short stature; Oral cleft; Abnormality of the face
Intellectual disability syndromic and non-syndromic v0.3244 KAT5 Zornitza Stark edited their review of gene: KAT5: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (NEDFASB), MIM#619103; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3244 H3F3B Zornitza Stark Phenotypes for gene: H3F3B were changed from to Intellectual disability; regression; seizures
Intellectual disability syndromic and non-syndromic v0.3243 H3F3B Zornitza Stark Publications for gene: H3F3B were set to
Intellectual disability syndromic and non-syndromic v0.3242 H3F3B Zornitza Stark Mode of inheritance for gene: H3F3B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3241 H3F3B Zornitza Stark Classified gene: H3F3B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3241 H3F3B Zornitza Stark Gene: h3f3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3240 H3F3B Zornitza Stark edited their review of gene: H3F3B: Added comment: 13 unrelated individuals reported with missense variants in H3F3B. Phenotype primarily comprised intellectual disability and minor congenital anomalies, regression in significant proportion. Seizures in 50%.; Changed rating: GREEN; Changed publications: 33268356; Changed phenotypes: Intellectual disability, regression, seizures; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3240 H3F3A Zornitza Stark Phenotypes for gene: H3F3A were changed from to Intellectual disability; regression; seizures
Intellectual disability syndromic and non-syndromic v0.3239 H3F3A Zornitza Stark Publications for gene: H3F3A were set to
Intellectual disability syndromic and non-syndromic v0.3238 H3F3A Zornitza Stark Mode of inheritance for gene: H3F3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3237 H3F3A Zornitza Stark Classified gene: H3F3A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3237 H3F3A Zornitza Stark Gene: h3f3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3236 H3F3A Zornitza Stark edited their review of gene: H3F3A: Added comment: 33 unrelated individuals reported with missense variants in H3F3A. Phenotype primarily comprised intellectual disability and minor congenital anomalies, regression in significant proportion. Seizures in 50%.; Changed rating: GREEN; Changed publications: 33268356; Changed phenotypes: Intellectual disability, regression, seizures; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3236 HIVEP2 Zornitza Stark Marked gene: HIVEP2 as ready
Intellectual disability syndromic and non-syndromic v0.3236 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3236 HIVEP2 Zornitza Stark Phenotypes for gene: HIVEP2 were changed from to Mental retardation, autosomal dominant 43, MIM# 616977
Intellectual disability syndromic and non-syndromic v0.3235 HIVEP2 Zornitza Stark Publications for gene: HIVEP2 were set to
Intellectual disability syndromic and non-syndromic v0.3234 HIVEP2 Zornitza Stark Mode of inheritance for gene: HIVEP2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3233 HIVEP2 Zornitza Stark reviewed gene: HIVEP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26153216, 27003583, 16836985, 31602191, 31207095; Phenotypes: Mental retardation, autosomal dominant 43, MIM# 616977; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3233 TFE3 Zornitza Stark Mode of inheritance for gene: TFE3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.3232 TFE3 Zornitza Stark Publications for gene: TFE3 were set to 30595499; 31833172
Intellectual disability syndromic and non-syndromic v0.3231 TFE3 Zornitza Stark Mode of pathogenicity for gene: TFE3 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.3230 TFE3 Zornitza Stark Mode of inheritance for gene: TFE3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3229 USP7 Zornitza Stark Phenotypes for gene: USP7 were changed from ID; Autism to Hao-Fountain syndrome, MIM# 616863; ID; Autism
Intellectual disability syndromic and non-syndromic v0.3228 USP7 Zornitza Stark Publications for gene: USP7 were set to 30679821
Intellectual disability syndromic and non-syndromic v0.3227 USP7 Zornitza Stark edited their review of gene: USP7: Changed publications: 26365382, 30679821
Intellectual disability syndromic and non-syndromic v0.3227 USP7 Zornitza Stark reviewed gene: USP7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hao-Fountain syndrome, MIM# 616863; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.3227 TFE3 Arina Puzriakova reviewed gene: TFE3: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 32409512; Phenotypes: TFE3-related intellectual disability with pigmentary mosaicism; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.3227 PIGK Zornitza Stark Marked gene: PIGK as ready
Intellectual disability syndromic and non-syndromic v0.3227 PIGK Zornitza Stark Gene: pigk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3227 PIGK Zornitza Stark Phenotypes for gene: PIGK were changed from Intellectual disability; seizures; cerebellar atrophy to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, MIM# 618879
Intellectual disability syndromic and non-syndromic v0.3226 PIGK Zornitza Stark edited their review of gene: PIGK: Changed phenotypes: Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, MIM# 618879
Intellectual disability syndromic and non-syndromic v0.3226 PIGB Zornitza Stark Phenotypes for gene: PIGB were changed from Epileptic encephalopathy, early infantile, 80; OMIM #618580 to Developmental and epileptic encephalopathy 80, MIM# 618580
Intellectual disability syndromic and non-syndromic v0.3225 PIGB Zornitza Stark reviewed gene: PIGB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 80, MIM# 618580; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3225 GPAA1 Zornitza Stark Marked gene: GPAA1 as ready
Intellectual disability syndromic and non-syndromic v0.3225 GPAA1 Zornitza Stark Gene: gpaa1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3225 GPAA1 Zornitza Stark Phenotypes for gene: GPAA1 were changed from to Glycosylphosphatidylinositol biosynthesis defect 15, MIM# 617810
Intellectual disability syndromic and non-syndromic v0.3224 GPAA1 Zornitza Stark Publications for gene: GPAA1 were set to
Intellectual disability syndromic and non-syndromic v0.3223 GPAA1 Zornitza Stark Mode of inheritance for gene: GPAA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3222 GPAA1 Zornitza Stark reviewed gene: GPAA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100095; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 15, MIM# 617810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3222 HDAC4 Bryony Thompson Classified gene: HDAC4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3222 HDAC4 Bryony Thompson Gene: hdac4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3221 HDAC4 Bryony Thompson reviewed gene: HDAC4: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1016/j.xhgg.2020.100015; Phenotypes: Intellectual disability, hypotonia, dysmorphism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3221 OGT Zornitza Stark Marked gene: OGT as ready
Intellectual disability syndromic and non-syndromic v0.3221 OGT Zornitza Stark Gene: ogt has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3221 OGT Zornitza Stark Phenotypes for gene: OGT were changed from to Mental retardation, X-linked 106, MIM# 300997
Intellectual disability syndromic and non-syndromic v0.3220 OGT Zornitza Stark Publications for gene: OGT were set to
Intellectual disability syndromic and non-syndromic v0.3219 OGT Zornitza Stark Mode of inheritance for gene: OGT was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3218 OGT Zornitza Stark reviewed gene: OGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302723, 28584052, 31296563, 31627256, 29769320, 29606577; Phenotypes: Mental retardation, X-linked 106, MIM# 300997; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3218 DPM2 Zornitza Stark Classified gene: DPM2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3218 DPM2 Zornitza Stark Gene: dpm2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3217 DPM2 Zornitza Stark edited their review of gene: DPM2: Added comment: Further unrelated individual reported, main clinical features were truncal hypotonia, hypertonicity, congenital heart defects, intellectual disability, and generalized muscle wasting.; Changed rating: GREEN; Changed publications: 23109149, 33129689
Intellectual disability syndromic and non-syndromic v0.3217 ALG9 Zornitza Stark Marked gene: ALG9 as ready
Intellectual disability syndromic and non-syndromic v0.3217 ALG9 Zornitza Stark Gene: alg9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3217 ALG9 Zornitza Stark Phenotypes for gene: ALG9 were changed from to Congenital disorder of glycosylation, type Il, MIM#608776
Intellectual disability syndromic and non-syndromic v0.3216 ALG9 Zornitza Stark Publications for gene: ALG9 were set to
Intellectual disability syndromic and non-syndromic v0.3215 ALG9 Zornitza Stark Mode of inheritance for gene: ALG9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3214 ALG8 Zornitza Stark Marked gene: ALG8 as ready
Intellectual disability syndromic and non-syndromic v0.3214 ALG8 Zornitza Stark Gene: alg8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3214 ALG8 Zornitza Stark Phenotypes for gene: ALG8 were changed from to Congenital disorder of glycosylation, type Ih, MIM# 608104
Intellectual disability syndromic and non-syndromic v0.3213 ALG8 Zornitza Stark Publications for gene: ALG8 were set to
Intellectual disability syndromic and non-syndromic v0.3212 ALG8 Zornitza Stark Mode of inheritance for gene: ALG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3211 ALG8 Zornitza Stark reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 26066342; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3211 ALG3 Zornitza Stark Marked gene: ALG3 as ready
Intellectual disability syndromic and non-syndromic v0.3211 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3211 ALG3 Zornitza Stark Phenotypes for gene: ALG3 were changed from to Congenital disorder of glycosylation, type Id, MIM# 601110
Intellectual disability syndromic and non-syndromic v0.3210 ALG3 Zornitza Stark Publications for gene: ALG3 were set to
Intellectual disability syndromic and non-syndromic v0.3209 ALG3 Zornitza Stark Mode of inheritance for gene: ALG3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3208 ALG3 Zornitza Stark reviewed gene: ALG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31067009; Phenotypes: Congenital disorder of glycosylation, type Id, MIM# 601110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3208 USP9X Zornitza Stark Marked gene: USP9X as ready
Intellectual disability syndromic and non-syndromic v0.3208 USP9X Zornitza Stark Gene: usp9x has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3208 USP9X Zornitza Stark Phenotypes for gene: USP9X were changed from to Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968)
Intellectual disability syndromic and non-syndromic v0.3207 USP9X Zornitza Stark Publications for gene: USP9X were set to
Intellectual disability syndromic and non-syndromic v0.3206 USP9X Zornitza Stark Mode of inheritance for gene: USP9X was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.3205 ALG6 Zornitza Stark Marked gene: ALG6 as ready
Intellectual disability syndromic and non-syndromic v0.3205 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3205 ALG6 Zornitza Stark Phenotypes for gene: ALG6 were changed from to Congenital disorder of glycosylation, type Ic (MIM#603147)
Intellectual disability syndromic and non-syndromic v0.3204 ALG6 Zornitza Stark Publications for gene: ALG6 were set to
Intellectual disability syndromic and non-syndromic v0.3203 ALG6 Zornitza Stark Mode of inheritance for gene: ALG6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3202 ALG6 Zornitza Stark reviewed gene: ALG6: Rating: GREEN; Mode of pathogenicity: None; Publications: 10914684, 27498540; Phenotypes: Congenital disorder of glycosylation, type Ic (MIM#603147); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3202 MOGS Zornitza Stark Marked gene: MOGS as ready
Intellectual disability syndromic and non-syndromic v0.3202 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3202 MOGS Zornitza Stark Phenotypes for gene: MOGS were changed from to Congenital disorder of glycosylation, type IIb, MIM# 606056
Intellectual disability syndromic and non-syndromic v0.3201 MOGS Zornitza Stark Publications for gene: MOGS were set to
Intellectual disability syndromic and non-syndromic v0.3200 MOGS Zornitza Stark Mode of inheritance for gene: MOGS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3199 MOGS Zornitza Stark reviewed gene: MOGS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31925597, 30587846, 33058492; Phenotypes: Congenital disorder of glycosylation, type IIb, MIM# 606056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3199 USP9X Paul De Fazio reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: None; Publications: 31443933, 26833328; Phenotypes: Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.3199 NEMF Zornitza Stark Phenotypes for gene: NEMF were changed from Intellectual disability; neuropathy to Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099; Intellectual disability; neuropathy
Intellectual disability syndromic and non-syndromic v0.3198 NEMF Zornitza Stark edited their review of gene: NEMF: Changed phenotypes: Intellectual developmental disorder with speech delay and axonal peripheral neuropathy, MIM# 619099, Intellectual disability, neuropathy
Intellectual disability syndromic and non-syndromic v0.3198 NARS Zornitza Stark Phenotypes for gene: NARS were changed from Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Intellectual disability syndromic and non-syndromic v0.3197 NARS Zornitza Stark Phenotypes for gene: NARS were changed from Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092; Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Intellectual disability syndromic and non-syndromic v0.3196 NARS Zornitza Stark reviewed gene: NARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities (NEDMILG), MIM#619091, Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG), MIM#619092, Abnormal muscle tone, Microcephaly, Global developmental delay, Intellectual disability, Seizures, Ataxia, Abnormality of the face, Demyelinating peripheral neuropathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3196 RLIM Zornitza Stark Marked gene: RLIM as ready
Intellectual disability syndromic and non-syndromic v0.3196 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3196 RLIM Zornitza Stark Phenotypes for gene: RLIM were changed from to Tonne-Kalscheuer syndrome, MIM# 300978
Intellectual disability syndromic and non-syndromic v0.3195 RLIM Zornitza Stark Publications for gene: RLIM were set to
Intellectual disability syndromic and non-syndromic v0.3194 RLIM Zornitza Stark Mode of inheritance for gene: RLIM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3193 RLIM Zornitza Stark reviewed gene: RLIM: Rating: GREEN; Mode of pathogenicity: None; Publications: 29728705, 25735484, 25644381; Phenotypes: Tonne-Kalscheuer syndrome, MIM# 300978; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3193 B4GALT7 Zornitza Stark Marked gene: B4GALT7 as ready
Intellectual disability syndromic and non-syndromic v0.3193 B4GALT7 Zornitza Stark Gene: b4galt7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3193 B4GALT7 Zornitza Stark Phenotypes for gene: B4GALT7 were changed from to Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070
Intellectual disability syndromic and non-syndromic v0.3192 B4GALT7 Zornitza Stark Publications for gene: B4GALT7 were set to
Intellectual disability syndromic and non-syndromic v0.3191 B4GALT7 Zornitza Stark Mode of inheritance for gene: B4GALT7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3190 B4GALT7 Zornitza Stark reviewed gene: B4GALT7: Rating: AMBER; Mode of pathogenicity: None; Publications: 23956117, 24755949, 31278392, 31614862, 31862401; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3190 MAPK1 Zornitza Stark Phenotypes for gene: MAPK1 were changed from Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin to Noonan syndrome 13, MIM#619087; Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin
Intellectual disability syndromic and non-syndromic v0.3189 MAPK1 Zornitza Stark reviewed gene: MAPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 13, MIM#619087, Global developmental delay, Intellectual disability, Behavioral abnormality, Growth delay, Abnormality of the face, Abnormality of the neck, Abnormality of the cardiovascular system, Abnormality of the skin; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3189 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome, MIM#619080; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies to Delpire-McNeill syndrome, MIM# 619083; Kilquist syndrome, MIM#619080; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.3188 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Delpire-McNeill syndrome, MIM# 619083, Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.3188 SLC12A2 Zornitza Stark Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies to Kilquist syndrome, MIM#619080; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.3187 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.3187 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Intellectual disability syndromic and non-syndromic v0.3187 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3187 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from to Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Intellectual disability syndromic and non-syndromic v0.3186 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Intellectual disability syndromic and non-syndromic v0.3185 JAM3 Zornitza Stark Mode of inheritance for gene: JAM3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3184 JAM3 Zornitza Stark reviewed gene: JAM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255084, 21109224; Phenotypes: Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3184 NCKAP1 Zornitza Stark Marked gene: NCKAP1 as ready
Intellectual disability syndromic and non-syndromic v0.3184 NCKAP1 Zornitza Stark Gene: nckap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3184 NCKAP1 Zornitza Stark Phenotypes for gene: NCKAP1 were changed from to Intellectual disability; autism
Intellectual disability syndromic and non-syndromic v0.3183 NCKAP1 Zornitza Stark Publications for gene: NCKAP1 were set to
Intellectual disability syndromic and non-syndromic v0.3182 NCKAP1 Zornitza Stark Mode of inheritance for gene: NCKAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3181 NCKAP1 Zornitza Stark reviewed gene: NCKAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33157009; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3181 ACAD9 Zornitza Stark Marked gene: ACAD9 as ready
Intellectual disability syndromic and non-syndromic v0.3181 ACAD9 Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3181 ACAD9 Zornitza Stark Phenotypes for gene: ACAD9 were changed from to Mitochondrial complex I deficiency, nuclear type 20 MIM#611126
Intellectual disability syndromic and non-syndromic v0.3180 ACAD9 Zornitza Stark Publications for gene: ACAD9 were set to
Intellectual disability syndromic and non-syndromic v0.3179 ACAD9 Zornitza Stark Mode of inheritance for gene: ACAD9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3178 ACAD9 Zornitza Stark reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30025539; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 MIM#611126; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3178 ITFG2 Zornitza Stark Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z
Intellectual disability syndromic and non-syndromic v0.3177 ITFG2 Zornitza Stark edited their review of gene: ITFG2: Changed rating: AMBER; Changed publications: 33083013; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3177 UNC80 Zornitza Stark Marked gene: UNC80 as ready
Intellectual disability syndromic and non-syndromic v0.3177 UNC80 Zornitza Stark Gene: unc80 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3177 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Intellectual disability syndromic and non-syndromic v0.3176 UNC80 Zornitza Stark Publications for gene: UNC80 were set to 26708751; 26708753; 26545877; 32620897; 30167850; 30167850
Intellectual disability syndromic and non-syndromic v0.3176 UNC80 Zornitza Stark Publications for gene: UNC80 were set to
Intellectual disability syndromic and non-syndromic v0.3175 UNC80 Zornitza Stark edited their review of gene: UNC80: Changed phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777
Intellectual disability syndromic and non-syndromic v0.3175 UNC80 Zornitza Stark Mode of inheritance for gene: UNC80 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3174 UNC80 Zornitza Stark reviewed gene: UNC80: Rating: GREEN; Mode of pathogenicity: None; Publications: 26708751, 26708753, 26545877, 32620897, 30167850, 30167850; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3174 ZFHX4 Zornitza Stark Tag SV/CNV tag was added to gene: ZFHX4.
Intellectual disability syndromic and non-syndromic v0.3174 ZFHX4 Zornitza Stark Classified gene: ZFHX4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3174 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3173 ZFHX4 Zornitza Stark gene: ZFHX4 was added
gene: ZFHX4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to 33057194; 24038936; 21802062
Phenotypes for gene: ZFHX4 were set to Developmental disorders; intellectual disability, dysmorphic features
Review for gene: ZFHX4 was set to GREEN
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 24038936 - a single case with developmental delay, macrocephaly, ventriculomegaly, hypermetropia, recurrent infections, dysmorphism and a de novo deletion of the last 7 exons of the gene.
PMID:21802062 (2011) report 8 individuals with ID and overlapping deletions of 8q21.11 (0.66-13.55 Mb in size); the smallest region of overlap encompasses 3 genes including ZFHX4.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3172 UPF1 Zornitza Stark Marked gene: UPF1 as ready
Intellectual disability syndromic and non-syndromic v0.3172 UPF1 Zornitza Stark Gene: upf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3172 UPF1 Zornitza Stark Classified gene: UPF1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3172 UPF1 Zornitza Stark Gene: upf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3171 UPF1 Zornitza Stark gene: UPF1 was added
gene: UPF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UPF1 were set to 33057194
Phenotypes for gene: UPF1 were set to Developmental disorders
Review for gene: UPF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (1 frameshift, 11 missense, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3170 U2AF2 Zornitza Stark Marked gene: U2AF2 as ready
Intellectual disability syndromic and non-syndromic v0.3170 U2AF2 Zornitza Stark Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3170 U2AF2 Zornitza Stark Classified gene: U2AF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3170 U2AF2 Zornitza Stark Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3169 U2AF2 Zornitza Stark gene: U2AF2 was added
gene: U2AF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: U2AF2 were set to 33057194
Phenotypes for gene: U2AF2 were set to Developmental disorders
Review for gene: U2AF2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 8 missense, 1 synoymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3168 TCF7L2 Zornitza Stark Marked gene: TCF7L2 as ready
Intellectual disability syndromic and non-syndromic v0.3168 TCF7L2 Zornitza Stark Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3168 TCF7L2 Zornitza Stark Classified gene: TCF7L2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3168 TCF7L2 Zornitza Stark Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3167 TCF7L2 Zornitza Stark gene: TCF7L2 was added
gene: TCF7L2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TCF7L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TCF7L2 were set to 33057194
Phenotypes for gene: TCF7L2 were set to Developmental disorders
Review for gene: TCF7L2 was set to AMBER
Added comment: A diabetes susceptibility locus associated with common SNVs, see OMIM for details.

PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo variants (2 frameshift, 6 missense, 1 splice acceptor, 2 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3166 SRRM2 Zornitza Stark Marked gene: SRRM2 as ready
Intellectual disability syndromic and non-syndromic v0.3166 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3166 SRRM2 Zornitza Stark Classified gene: SRRM2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3166 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3165 SRRM2 Zornitza Stark gene: SRRM2 was added
gene: SRRM2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SRRM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM2 were set to 33057194
Phenotypes for gene: SRRM2 were set to Developmental disorders
Review for gene: SRRM2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 28 de novo variants (11 frameshift, 7 missense, 1 splice acceptor, 5 stopgain, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3164 SPEN Zornitza Stark Marked gene: SPEN as ready
Intellectual disability syndromic and non-syndromic v0.3164 SPEN Zornitza Stark Gene: spen has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3164 SPEN Zornitza Stark Classified gene: SPEN as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3164 SPEN Zornitza Stark Gene: spen has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3163 SPEN Zornitza Stark gene: SPEN was added
gene: SPEN was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPEN were set to 33057194
Phenotypes for gene: SPEN were set to Developmental disorders
Review for gene: SPEN was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 25 de novo variants (6 frameshift, 1 in-frame, 7 missense, 8 stopgain, 3 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3162 SATB1 Zornitza Stark Marked gene: SATB1 as ready
Intellectual disability syndromic and non-syndromic v0.3162 SATB1 Zornitza Stark Gene: satb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3162 SATB1 Zornitza Stark Classified gene: SATB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3162 SATB1 Zornitza Stark Gene: satb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3161 SATB1 Zornitza Stark gene: SATB1 was added
gene: SATB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB1 were set to 33057194
Phenotypes for gene: SATB1 were set to Developmental disorders
Review for gene: SATB1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo (2 frameshift, 7 missense, 1 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3160 RAB14 Zornitza Stark Marked gene: RAB14 as ready
Intellectual disability syndromic and non-syndromic v0.3160 RAB14 Zornitza Stark Gene: rab14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3160 RAB14 Zornitza Stark Classified gene: RAB14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3160 RAB14 Zornitza Stark Gene: rab14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3159 RAB14 Zornitza Stark gene: RAB14 was added
gene: RAB14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAB14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB14 were set to 33057194
Phenotypes for gene: RAB14 were set to Developmental disorders
Review for gene: RAB14 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (1 in-frame, 7 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Marked gene: PSMC5 as ready
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Classified gene: PSMC5 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3157 PSMC5 Zornitza Stark gene: PSMC5 was added
gene: PSMC5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC5 were set to 33057194
Phenotypes for gene: PSMC5 were set to Developmental disorders
Review for gene: PSMC5 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 9 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3156 MSL2 Zornitza Stark Marked gene: MSL2 as ready
Intellectual disability syndromic and non-syndromic v0.3156 MSL2 Zornitza Stark Gene: msl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3156 MSL2 Zornitza Stark Classified gene: MSL2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3156 MSL2 Zornitza Stark Gene: msl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3155 MSL2 Zornitza Stark gene: MSL2 was added
gene: MSL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MSL2 were set to 31332282; 33057194
Phenotypes for gene: MSL2 were set to Developmental disorders; autism
Review for gene: MSL2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 13 de novo variants (9 frameshift, 4 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
PMID: 31332282 - candidate gene in a single autism study, with recurrent de novo variants in a potential oligogenic model
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3154 MMGT1 Zornitza Stark Marked gene: MMGT1 as ready
Intellectual disability syndromic and non-syndromic v0.3154 MMGT1 Zornitza Stark Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3154 MMGT1 Zornitza Stark Classified gene: MMGT1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3154 MMGT1 Zornitza Stark Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3153 MMGT1 Zornitza Stark gene: MMGT1 was added
gene: MMGT1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MMGT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MMGT1 were set to 33057194
Phenotypes for gene: MMGT1 were set to Developmental disorders
Review for gene: MMGT1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 3 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3152 HNRNPD Zornitza Stark Marked gene: HNRNPD as ready
Intellectual disability syndromic and non-syndromic v0.3152 HNRNPD Zornitza Stark Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3152 HNRNPD Zornitza Stark Classified gene: HNRNPD as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3152 HNRNPD Zornitza Stark Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3151 HNRNPD Zornitza Stark gene: HNRNPD was added
gene: HNRNPD was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HNRNPD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPD were set to 33057194
Phenotypes for gene: HNRNPD were set to Developmental disorders
Review for gene: HNRNPD was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (5 frameshift, 1 missense, 1 splice acceptor, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3150 GIGYF1 Zornitza Stark Marked gene: GIGYF1 as ready
Intellectual disability syndromic and non-syndromic v0.3150 GIGYF1 Zornitza Stark Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3150 GIGYF1 Zornitza Stark Classified gene: GIGYF1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3150 GIGYF1 Zornitza Stark Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3149 GIGYF1 Zornitza Stark gene: GIGYF1 was added
gene: GIGYF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GIGYF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIGYF1 were set to 33057194
Phenotypes for gene: GIGYF1 were set to Developmental disorder
Review for gene: GIGYF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3148 AP2S1 Zornitza Stark Marked gene: AP2S1 as ready
Intellectual disability syndromic and non-syndromic v0.3148 AP2S1 Zornitza Stark Gene: ap2s1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3148 AP2S1 Zornitza Stark Classified gene: AP2S1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3148 AP2S1 Zornitza Stark Gene: ap2s1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3147 AP2S1 Zornitza Stark gene: AP2S1 was added
gene: AP2S1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AP2S1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AP2S1 were set to 33057194
Phenotypes for gene: AP2S1 were set to Developmental disorder
Review for gene: AP2S1 was set to AMBER
Added comment: Established hypercalcaemia gene. PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 5 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3146 ARHGAP35 Zornitza Stark Marked gene: ARHGAP35 as ready
Intellectual disability syndromic and non-syndromic v0.3146 ARHGAP35 Zornitza Stark Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3146 ARHGAP35 Zornitza Stark Classified gene: ARHGAP35 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3146 ARHGAP35 Zornitza Stark Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3145 ARHGAP35 Zornitza Stark gene: ARHGAP35 was added
gene: ARHGAP35 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP35 were set to 33057194
Phenotypes for gene: ARHGAP35 were set to Developmental disorder
Review for gene: ARHGAP35 was set to AMBER
Added comment: Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 16 de novo variants (3 frameshift, 2 in-frame, 10 missense, 1 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3144 ATP6V0A1 Zornitza Stark Marked gene: ATP6V0A1 as ready
Intellectual disability syndromic and non-syndromic v0.3144 ATP6V0A1 Zornitza Stark Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3144 ATP6V0A1 Zornitza Stark Classified gene: ATP6V0A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3144 ATP6V0A1 Zornitza Stark Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3143 ATP6V0A1 Zornitza Stark gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0A1 were set to 30842224; 33057194
Phenotypes for gene: ATP6V0A1 were set to Developmental disorder; Rett syndrome-like
Review for gene: ATP6V0A1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 11 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
PMID: 30842224 - identified a de novo missense variant in a single individual with atypical Rett syndrome phenotype
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3142 DDX23 Zornitza Stark Marked gene: DDX23 as ready
Intellectual disability syndromic and non-syndromic v0.3142 DDX23 Zornitza Stark Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3142 DDX23 Zornitza Stark Classified gene: DDX23 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3142 DDX23 Zornitza Stark Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3141 DDX23 Zornitza Stark gene: DDX23 was added
gene: DDX23 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DDX23 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX23 were set to 33057194
Phenotypes for gene: DDX23 were set to Developmental disorder
Review for gene: DDX23 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 6 de novo missense identified in ~10,000 cases with developmental disorders. Rated Amber as no other phenotype info provided.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3140 FOXP4 Zornitza Stark Marked gene: FOXP4 as ready
Intellectual disability syndromic and non-syndromic v0.3140 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3140 FOXP4 Zornitza Stark Classified gene: FOXP4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3140 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3139 FOXP4 Zornitza Stark edited their review of gene: FOXP4: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.3139 FOXP4 Zornitza Stark changed review comment from: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early challenges.
Sources: Literature; to: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3139 FOXP4 Zornitza Stark changed review comment from: Six unrelated individuals reported, 5 with missense variants in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis.
Sources: Literature; to: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early challenges.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3139 FOXP4 Zornitza Stark gene: FOXP4 was added
gene: FOXP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to GREEN
Added comment: Six unrelated individuals reported, 5 with missense variants in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3138 DHX32 Zornitza Stark Marked gene: DHX32 as ready
Intellectual disability syndromic and non-syndromic v0.3138 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3138 DHX32 Zornitza Stark Classified gene: DHX32 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3138 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3137 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant
Intellectual disability syndromic and non-syndromic v0.3136 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979 to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant
Intellectual disability syndromic and non-syndromic v0.3135 FBXO31 Zornitza Stark Publications for gene: FBXO31 were set to 24623383
Intellectual disability syndromic and non-syndromic v0.3134 FBXO31 Zornitza Stark Mode of pathogenicity for gene: FBXO31 was changed from to Other
Intellectual disability syndromic and non-syndromic v0.3133 FBXO31 Zornitza Stark Classified gene: FBXO31 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3133 FBXO31 Zornitza Stark Gene: fbxo31 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3132 DHX32 Dean Phelan gene: DHX32 was added
gene: DHX32 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DHX32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX32 were set to PMID: 32989326
Phenotypes for gene: DHX32 were set to Intellectual disability, spastic diplegia, dystonia, brain abnormalities
Review for gene: DHX32 was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two unrelated patients with intellectual disability, one with spastic diplegia, and the other characterised as generalised dystonia. Brain abnormalities were identified also.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3132 FBXO31 Kristin Rigbye reviewed gene: FBXO31: Rating: AMBER; Mode of pathogenicity: Other; Publications: PMID: 32989326; Phenotypes: Mental retardation, autosomal recessive 45, MIM#615979, Cerebral palsy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3132 STN1 Sue White Classified gene: STN1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3132 STN1 Sue White Gene: stn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3131 STN1 Sue White gene: STN1 was added
gene: STN1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 32627942; 27432940
Phenotypes for gene: STN1 were set to cerebral calcification; premature ageing; bone marrow failure; retinal telangiactasia; hepatic fibrosis
Penetrance for gene: STN1 were set to Complete
Added comment: 3 unrelated patients reported with Coats-plus syndrome. Developmental delay noted in two.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3130 TKFC Zornitza Stark Phenotypes for gene: TKFC were changed from Developmental delay; cataracts; liver dysfunction to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction
Intellectual disability syndromic and non-syndromic v0.3129 TKFC Zornitza Stark edited their review of gene: TKFC: Changed phenotypes: Triokinase and FMN cyclase deficiency syndrome, MIM#618805, Developmental delay, cataracts, liver dysfunction
Intellectual disability syndromic and non-syndromic v0.3129 PRKAR1B Zornitza Stark Marked gene: PRKAR1B as ready
Intellectual disability syndromic and non-syndromic v0.3129 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3129 PRKAR1B Zornitza Stark Classified gene: PRKAR1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3129 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3128 PRKAR1B Konstantinos Varvagiannis edited their review of gene: PRKAR1B: Changed publications: https://doi.org/10.1101/2020.09.10.20190314, 25414040
Intellectual disability syndromic and non-syndromic v0.3128 PRKAR1B Konstantinos Varvagiannis gene: PRKAR1B was added
gene: PRKAR1B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRKAR1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 33057194
Phenotypes for gene: PRKAR1B were set to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Penetrance for gene: PRKAR1B were set to unknown
Review for gene: PRKAR1B was set to AMBER
Added comment: Please consider inclusion of this gene with amber rating pending publication of the preprint and/or additional evidence.

Marbach et al. (2020 - medRxiv : https://doi.org/10.1101/2020.09.10.20190314 - last author : C. Schaaf) report 6 unrelated individuals with heterozygous missense PRKAR1B variants.

All presented formal ASD diagnosis (6/6), global developmental delay (6/6) and intellectual disability (all - formal evaluations were lacking though). Additional features included neurologic anomalies (movement disorders : dyspraxia, apraxia, clumsiness in all, with tremor/dystonia or involuntary movements as single occurrences). Three displayed high pain tolerance. Regression in speech was a feature in two. Additional behavior anomalies included ADHD (4-5/6) or aggression (3/6). There was no consistent pattern of malformations, physical anomalies or facial features (with the exception of uplsanted palpebral fissures reported in 4).

3 different missense variants were identified (NM_00116470:c.1003C>T - p.Arg335Trp, c.586G>A - p.Glu196Lys, c.500_501delAAinsTT - p.Gln167Leu) with Arg355Trp being a recurrent one within this cohort (4/6 subjects). A possible splicing effect may apply for the MNV. All variants are absent from gnomAD and the SNVs had CADD scores > 24.

In all cases were parental samples were available (5/6), the variant had occurred as a de novo event.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes. As the authors comment, the RIβ subunit is primarily expressed in brain with higher expression in cortex and hypothalamus.

The functional consequences of the variants at cellular level were not studied.

Previous studies have demonstrated that downregulation of RIβ in murine hippocampal cultures, reduced phosphorylation of CREB, a transcription factor involved in long-term memory formation. The authors speculate that a similar effect on cAMP/PKA/CREB cascade may mediate the cognitive effects in humans. RIβ deficient mice also display diminished nociceptive pain, similar to the human phenotype. [Several refs provided].

The authors cite the study by Kaplanis et al (2020 - PMID: 33057194), where in a large sample of 31,058 trio exomes of children with developmental disorders, PRKAR1B was among the genes with significant enrichment for de novo missense variants. [The gene has a pLI score of 0.18 in gnomAD / o/e = 0.26 - so pLoF variants may not be deleterious].

Please note that a specific PRKAR1B variant (NM_002735.2:c.149T>G - p.Leu50Arg) has been previous reported to segregate with a late-onset neurodegenerative disorder characterized by dementia and/or parkinsonism within a large pedigree with 12 affected individuals [Wong et al 2014 - PMID: 25414040].
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3128 MPP5 Zornitza Stark Marked gene: MPP5 as ready
Intellectual disability syndromic and non-syndromic v0.3128 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3128 MPP5 Zornitza Stark Classified gene: MPP5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3128 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3127 MPP5 Konstantinos Varvagiannis gene: MPP5 was added
gene: MPP5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MPP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MPP5 were set to 33073849
Phenotypes for gene: MPP5 were set to Global developmental delay; Intellectual disability; Delayed speech and language development; Developmental regression; Behavioral abnormality
Penetrance for gene: MPP5 were set to unknown
Review for gene: MPP5 was set to GREEN
Added comment: Sterling et al (2020 - PMID: 33073849) provide information on the phenotype of 3 individuals with de novo MPP5 variants.

Common features included global developmental delay, intellectual disability (3/3 - severe in 2/3), speech delay/regression (the latter in at least 2) and behavioral abnormalities. Variable other features were reported, among others microcephaly (1/3), abnormal vision (1/3 : CVI, retinal dystrophy, nystagmus), brain MRI abnormalities (2/3), late-onset seizures (1/3). These subjects displayed variable and non-specific dysmorphic features.

All were investigated by exome sequencing (previous investigations not mentioned).

One subject was found to harbor a de novo mosaic (5/25 reads) stopgain variant, further confirmed by Sanger sequencing [NM_022474.4:c.1555C>T - p.(Arg519Ter). The specific variant is reported once in gnomAD (1/251338). Two de novo missense variants were identified in the remaining individuals [c.1289A>G - p.Glu430Gly / c.974A>C - p.His325Pro). All variants had in silico predictions in favor of a deleterious effect (CADD score >24).

The authors comment that MPP5 encodes an apical complex protein with asymmetric localization to the apical side of polarized cells. It is expressed in brain, peripheral nervous system and other tissues. MPP5 is a member of the membrane-associated guanylate kinase family of proteins (MAGUK p55 subfamily), determining cell polarity at tight junctions.

Previous animal models suggest that complete Mpp5(Pals1) KO in mice leads to near absence of cerebral cortical neurons. Htz KO display reduction in size of cerebral cortex and hippocampus. The gene is expressed in proliferating cell populations of cerebellum and important for establishment cerebellar architecture. Conditional KO of Mpp5(Pals1) in retinal progenitor cells mimics the retinal pathology observed in LCA. [Several refs. provided]

The authors studied a heterozygous CNS-specific Mpp5 KO mouse model. These mice presented microcephaly, decreased cerebellar volume and cortical thickness, decreased ependymal cells and Mpp5 at the apical surface of cortical vertrical zone. The proportion of cortical cells undergoing apoptotic cell death was increased. Mice displayed behavioral abnormalities (hyperactivity) and visual deficits, with ERG traces further suggesting retinal blindness.

Overall the mouse model was thought to recapitulate the behavioral abnormalities observed in affected subjects as well as individual rare features such as microcephaly and abnormal vision.

Haploinsufficiency (rather than a dominant negative effect) is favored as the underlying disease mechanism. This is also in line with a dose dependent effect observed in mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3127 ODC1 Zornitza Stark Publications for gene: ODC1 were set to 30475435
Intellectual disability syndromic and non-syndromic v0.3126 ODC1 Zornitza Stark edited their review of gene: ODC1: Added comment: Fifth individual reported in PMID 30239107: de novo nonsense variant identified, molecular modeling suggested that due to lack of a C terminus in the mutant protein, antizyme binding does not induce ODC degradation, leading to accumulation of active protein.; Changed publications: 30475435, 30239107
Intellectual disability syndromic and non-syndromic v0.3126 ODC1 Zornitza Stark Phenotypes for gene: ODC1 were changed from Intellectual disability; macrocephaly; dysmorphism to Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3125 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: Neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3125 ODC1 Zornitza Stark edited their review of gene: ODC1: Changed phenotypes: neurodevelopmental disorder with alopecia and brain imaging abnormalities (NEDABIA), MIM#619075
Intellectual disability syndromic and non-syndromic v0.3125 LRRC32 Zornitza Stark Phenotypes for gene: LRRC32 were changed from Intellectual disability; cleft palate; proliferative retinopathy to Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Intellectual disability syndromic and non-syndromic v0.3124 LRRC32 Zornitza Stark edited their review of gene: LRRC32: Changed phenotypes: Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD) syndrome, MIM# 619074
Intellectual disability syndromic and non-syndromic v0.3124 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy; intellectual disability to Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Intellectual disability syndromic and non-syndromic v0.3123 NUS1 Zornitza Stark edited their review of gene: NUS1: Changed phenotypes: Mental retardation, autosomal dominant 55, with seizures, MIM# 617831
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Marked gene: COG8 as ready
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3123 COG8 Zornitza Stark Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh, MIM# 611182
Intellectual disability syndromic and non-syndromic v0.3122 COG8 Zornitza Stark Publications for gene: COG8 were set to
Intellectual disability syndromic and non-syndromic v0.3121 COG8 Zornitza Stark Mode of inheritance for gene: COG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3120 COG8 Zornitza Stark changed review comment from: Four unrelated families reported with bi-allelic LOF variants and a broad range of predominantly neurological features (ID, seizures, arthrogryposis, brain malformations).

ID present in 3/4, presentation in the 4th family was antenatal but with severe neurological phenotype that would have been expected to result in ID.; to: Four unrelated families reported with bi-allelic LOF variants and a broad range of predominantly neurological features (ID, seizures, arthrogryposis, brain malformations).

ID reported in 3/4, presentation in the 4th family was antenatal but with severe neurological phenotype that would have been expected to result in ID.
Intellectual disability syndromic and non-syndromic v0.3120 COG8 Zornitza Stark reviewed gene: COG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17220172, 28619360, 30690882, 17331980; Phenotypes: Congenital disorder of glycosylation, type IIh, MIM# 611182; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3120 SLC35A3 Zornitza Stark Phenotypes for gene: SLC35A3 were changed from ?Arthrogryposis, mental retardation, and seizures; OMIM #615553 to Arthrogryposis, mental retardation, and seizures OMIM #615553; Skeletal dysplasia
Intellectual disability syndromic and non-syndromic v0.3119 SLC35A3 Zornitza Stark Publications for gene: SLC35A3 were set to PMID: 28328131; 24031089
Intellectual disability syndromic and non-syndromic v0.3118 SLC35A3 Zornitza Stark reviewed gene: SLC35A3: Rating: AMBER; Mode of pathogenicity: None; Publications: 28777481; Phenotypes: Skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Marked gene: APOPT1 as ready
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Gene: apopt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3118 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061 to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Intellectual disability syndromic and non-syndromic v0.3117 APOPT1 Zornitza Stark Phenotypes for gene: APOPT1 were changed from to Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061
Intellectual disability syndromic and non-syndromic v0.3116 APOPT1 Zornitza Stark Publications for gene: APOPT1 were set to
Intellectual disability syndromic and non-syndromic v0.3115 APOPT1 Zornitza Stark Mode of inheritance for gene: APOPT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3114 APOPT1 Zornitza Stark reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 17, MIM#619061; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3114 COA3 Zornitza Stark Phenotypes for gene: COA3 were changed from Mitochondrial complex IV deficiency to Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Intellectual disability syndromic and non-syndromic v0.3113 COA3 Zornitza Stark edited their review of gene: COA3: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 14, MIM# 619058
Intellectual disability syndromic and non-syndromic v0.3113 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from Mitochondrial complex IV deficiency, MIM# 220110 to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Intellectual disability syndromic and non-syndromic v0.3112 PET100 Zornitza Stark Tag founder tag was added to gene: PET100.
Intellectual disability syndromic and non-syndromic v0.3112 PET100 Zornitza Stark edited their review of gene: PET100: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Intellectual disability syndromic and non-syndromic v0.3112 COX14 Zornitza Stark Phenotypes for gene: COX14 were changed from Mitochondrial complex IV deficiency, MIM#220110 to Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Intellectual disability syndromic and non-syndromic v0.3111 COX14 Zornitza Stark edited their review of gene: COX14: Changed phenotypes: Mitochondrial complex IV deficiency, nuclear type 10, MIM#619053
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Marked gene: PRKACB as ready
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Gene: prkacb has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Classified gene: PRKACB as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3111 PRKACB Zornitza Stark Gene: prkacb has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Marked gene: COX6B1 as ready
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3110 COX6B1 Zornitza Stark Phenotypes for gene: COX6B1 were changed from to Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051
Intellectual disability syndromic and non-syndromic v0.3109 COX6B1 Zornitza Stark Publications for gene: COX6B1 were set to
Intellectual disability syndromic and non-syndromic v0.3108 COX6B1 Zornitza Stark Mode of inheritance for gene: COX6B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3107 COX6B1 Zornitza Stark Classified gene: COX6B1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3107 COX6B1 Zornitza Stark Gene: cox6b1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3106 COX6B1 Zornitza Stark reviewed gene: COX6B1: Rating: RED; Mode of pathogenicity: None; Publications: 18499082, 24781756; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 7, MIM# 619051; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Marked gene: SCO1 as ready
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3106 SCO1 Zornitza Stark Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048
Intellectual disability syndromic and non-syndromic v0.3105 SCO1 Zornitza Stark Publications for gene: SCO1 were set to
Intellectual disability syndromic and non-syndromic v0.3104 SCO1 Zornitza Stark Mode of inheritance for gene: SCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3103 SCO1 Zornitza Stark Classified gene: SCO1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3103 SCO1 Zornitza Stark Gene: sco1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3102 SCO1 Zornitza Stark reviewed gene: SCO1: Rating: RED; Mode of pathogenicity: None; Publications: 11013136, 19295170, 31352446, 23878101; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 4, MIM# 619048; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3102 PRKACB Konstantinos Varvagiannis edited their review of gene: PRKACB: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.3102 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to Complete
Review for gene: PRKACB was set to AMBER
Added comment: ID was a feature in 2/4 individuals with PRKACB pathogenic variant reported to date.
------
Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Marked gene: COX10 as ready
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Gene: cox10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3102 COX10 Zornitza Stark Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046
Intellectual disability syndromic and non-syndromic v0.3101 COX10 Zornitza Stark Publications for gene: COX10 were set to
Intellectual disability syndromic and non-syndromic v0.3100 COX10 Zornitza Stark Mode of inheritance for gene: COX10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3099 COX10 Zornitza Stark reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3099 DPH1 Zornitza Stark Publications for gene: DPH1 were set to 25558065; 26220823
Intellectual disability syndromic and non-syndromic v0.3098 DPH1 Zornitza Stark edited their review of gene: DPH1: Added comment: Four unrelated families reported, 11 affected individuals. Common clinical features include abnormal skull shape (trigonocephaly, scaphocephaly, or prominent forehead accompanied with metopic ridge), distinctive face (downslanted palpebral fissures, low set ears, depressed nasal bridge, and sparse hair on the scalp, eyelashes, and/or eyebrows), short stature, developmental delay, and intellectual disability. Heart and brain malformations are also frequently observed.; Changed publications: 29362492, 29410513, 25558065, 26220823
Intellectual disability syndromic and non-syndromic v0.3098 SETD1A Zornitza Stark changed review comment from: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; to: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.
Intellectual disability syndromic and non-syndromic v0.3098 SETD1A Zornitza Stark Phenotypes for gene: SETD1A were changed from Epilepsy, early-onset, with or without developmental delay, MIM# 618832 to Epilepsy, early-onset, with or without developmental delay, MIM# 618832; Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Intellectual disability syndromic and non-syndromic v0.3097 SETD1A Zornitza Stark edited their review of gene: SETD1A: Added comment: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 3 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; Changed phenotypes: Epilepsy, early-onset, with or without developmental delay, MIM# 618832, Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Intellectual disability syndromic and non-syndromic v0.3097 JARID2 Zornitza Stark Publications for gene: JARID2 were set to 23294540
Intellectual disability syndromic and non-syndromic v0.3096 JARID2 Zornitza Stark Tag SV/CNV tag was added to gene: JARID2.
Intellectual disability syndromic and non-syndromic v0.3096 JARID2 Zornitza Stark Classified gene: JARID2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3096 JARID2 Zornitza Stark Gene: jarid2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3095 JARID2 Zornitza Stark changed review comment from: 13 additional individuals reported, note CNVs common.; to: 13 additional individuals reported, note CNVs common but LOF sequence variants identified too.
Intellectual disability syndromic and non-syndromic v0.3095 JARID2 Zornitza Stark edited their review of gene: JARID2: Added comment: 13 additional individuals reported, note CNVs common.; Changed rating: GREEN; Changed publications: 23294540, 33077894
Intellectual disability syndromic and non-syndromic v0.3095 NUDT2 Zornitza Stark Phenotypes for gene: NUDT2 were changed from Muscular hypotonia; Global developmental delay; Intellectual disability to Muscular hypotonia; Global developmental delay; Intellectual disability; Polyneuropathy
Intellectual disability syndromic and non-syndromic v0.3094 NUDT2 Zornitza Stark Publications for gene: NUDT2 were set to 27431290; 30059600
Intellectual disability syndromic and non-syndromic v0.3093 NUDT2 Zornitza Stark Classified gene: NUDT2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3093 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3092 NUDT2 Zornitza Stark changed review comment from: Two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype. Upgrade to Green.; to: Three individuals from two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype. Upgrade to Green.
Intellectual disability syndromic and non-syndromic v0.3092 NUDT2 Zornitza Stark edited their review of gene: NUDT2: Added comment: Two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype. Upgrade to Green.; Changed rating: GREEN; Changed publications: 27431290, 30059600, 33058507; Changed phenotypes: Muscular hypotonia, Global developmental delay, Intellectual disability, Polyneuropathy
Intellectual disability syndromic and non-syndromic v0.3092 AFF2 Zornitza Stark Marked gene: AFF2 as ready
Intellectual disability syndromic and non-syndromic v0.3092 AFF2 Zornitza Stark Gene: aff2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3092 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from to Mental retardation, X-linked, FRAXE type 309548
Intellectual disability syndromic and non-syndromic v0.3091 AFF2 Zornitza Stark Publications for gene: AFF2 were set to
Intellectual disability syndromic and non-syndromic v0.3090 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3089 AFF2 Zornitza Stark reviewed gene: AFF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8334699, 21739600, 22773736; Phenotypes: Mental retardation, X-linked, FRAXE type 309548; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3089 KANSL1 Zornitza Stark Tag SV/CNV tag was added to gene: KANSL1.
Intellectual disability syndromic and non-syndromic v0.3089 AUTS2 Zornitza Stark Marked gene: AUTS2 as ready
Intellectual disability syndromic and non-syndromic v0.3089 AUTS2 Zornitza Stark Gene: auts2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3089 AUTS2 Zornitza Stark Phenotypes for gene: AUTS2 were changed from to Mental retardation, autosomal dominant 26, MIM#615834
Intellectual disability syndromic and non-syndromic v0.3088 AUTS2 Zornitza Stark Publications for gene: AUTS2 were set to
Intellectual disability syndromic and non-syndromic v0.3087 AUTS2 Zornitza Stark Mode of inheritance for gene: AUTS2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3086 AUTS2 Zornitza Stark Tag SV/CNV tag was added to gene: AUTS2.
Intellectual disability syndromic and non-syndromic v0.3086 AUTS2 Zornitza Stark reviewed gene: AUTS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23332918, 25205402, 31474318; Phenotypes: Mental retardation, autosomal dominant 26, MIM#615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3086 ZEB2 Zornitza Stark Marked gene: ZEB2 as ready
Intellectual disability syndromic and non-syndromic v0.3086 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3086 ZEB2 Zornitza Stark Phenotypes for gene: ZEB2 were changed from to Mowat-Wilson syndrome (MIM#235730)
Intellectual disability syndromic and non-syndromic v0.3085 ZEB2 Zornitza Stark Publications for gene: ZEB2 were set to
Intellectual disability syndromic and non-syndromic v0.3084 ZEB2 Zornitza Stark Mode of inheritance for gene: ZEB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3083 ZEB2 Zornitza Stark reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29300384; Phenotypes: Mowat-Wilson syndrome (MIM#235730); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3083 HECW2 Zornitza Stark Publications for gene: HECW2 were set to 27389779
Intellectual disability syndromic and non-syndromic v0.3082 HECW2 Zornitza Stark Mode of pathogenicity for gene: HECW2 was changed from to Other
Intellectual disability syndromic and non-syndromic v0.3081 HECW2 Zornitza Stark reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 29807643, 29395664, 27334371, 27389779; Phenotypes: Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268, intellectual disability, epilepsy, regression, microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Marked gene: CSNK1G1 as ready
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Added comment: Comment when marking as ready: Borderline Green/Amber rating.
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Classified gene: CSNK1G1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3081 CSNK1G1 Zornitza Stark Gene: csnk1g1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3080 LMNB2 Zornitza Stark Marked gene: LMNB2 as ready
Intellectual disability syndromic and non-syndromic v0.3080 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3080 LMNB2 Zornitza Stark Classified gene: LMNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3080 LMNB2 Zornitza Stark Gene: lmnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3079 LMNB1 Zornitza Stark changed review comment from: Adult-onset neurodegenerative condition, not truly ID.; to: Adult-onset neurodegenerative condition, not truly ID. Associated with CNV of this gene, suggestive of haploinsufficiency.
Intellectual disability syndromic and non-syndromic v0.3079 LMNB1 Zornitza Stark Publications for gene: LMNB1 were set to 32910914
Intellectual disability syndromic and non-syndromic v0.3078 CSNK1G1 Konstantinos Varvagiannis changed review comment from: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presenting ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) are also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature; to: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presented ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) are also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 CSNK1G1 Konstantinos Varvagiannis changed review comment from: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presenting ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature; to: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presenting ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) are also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 CSNK1G1 Konstantinos Varvagiannis gene: CSNK1G1 was added
gene: CSNK1G1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CSNK1G1 were set to 33009664
Phenotypes for gene: CSNK1G1 were set to Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of the face; Abnromality of limbs
Penetrance for gene: CSNK1G1 were set to unknown
Review for gene: CSNK1G1 was set to AMBER
Added comment: Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presenting ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 LMNB2 Konstantinos Varvagiannis changed review comment from: Please consider inclusion of LMNB2 in the ID panel with amber/green rating.

Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) appart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occured at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]
Sources: Literature; to: Please consider inclusion of LMNB2 in the ID panel with amber/green rating.

Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) apart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occurred at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 LMNB2 Konstantinos Varvagiannis gene: LMNB2 was added
gene: LMNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LMNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LMNB2 were set to 33033404
Phenotypes for gene: LMNB2 were set to Congenital microcephaly; Global developmental delay; Intellectual disability
Penetrance for gene: LMNB2 were set to Complete
Mode of pathogenicity for gene: LMNB2 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: LMNB2 was set to GREEN
Added comment: Please consider inclusion of LMNB2 in the ID panel with amber/green rating.

Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) appart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occured at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3078 LMNB1 Konstantinos Varvagiannis commented on gene: LMNB1: There is an additional report on LMBN1/2-associated phenotypes supporting green rating of the gene in the current panel.

Parry et al (2020 - PMID: 33033404) in a study to identify novel microcephaly genes using the DDD and 100k genomes project (100kGP) patient cohort, report on the phenotype of 13 individuals with heterozygous variant in LMNB1 (N=7) and LMNB2 (N=6).

LMNB1 : The authors identified 3 recurrent variants (c.97A>G - p.Lys33Glu (3), c.97_99del - p.Lys33del (2) , c.269G>C - p.Arg90Pro (2) / NM_005573.4) in seven individuals (3 from the DDD study, 4 from the 100kGP). In all cases were segregation studies were possible, the variant had occurred as a de novo event.

LMNB2 : 4 individuals from the DDD cohort and 1 from the 100kGP were found to harbor the same missense SNV (NM_032737.4:c.1192G>A, p.Glu398Lys). The variant had occurred de novo in 3 subjects and was inherited from a mosaic - unaffected - parent in a further case. Another individual was found to harbor c.160A>C - p.Asn54His.

LMNB1/2 common phenotypes :
All cases had congenital microcephaly (OFC -5.85 +/- 1.14 SD) appart from one individual, without history of IUGR or postnatally abnormal height (the latter in most).

Neuroimaging suggested structurally normal brain without abnormal migration. Gyral simplification / global reduction in white matter / increased extra axial spaces / enlarged ventricles were reported in 2.

LMNB1 - Global developmental delay was a feature in all (mild to severe) with some having occasional words at 7y (P3), absent speech (P9 - age category 5-10y) or ID not further specified (P13).

LMNB2 - DD was a feature in all 6 subjects (5/6 moderate to severe - 1/6 GDD). 5/6 were 10y or older with language (in 3 language not achieved) and motor deficits (walking not achieved in 1/6 - occured at the age of 6y in 1/6).

Facial features were not consistent nor suggestive of a syndromic diagnosis (sloping forehead in some).

Overall, as the authors comment, the phenotype corresponded to a severe nonsyndromic microcephaly (although additional features were reported in some).

Animal model:
Microcephaly is supported by Lmnb1 ko mouse model. Lmnb1/2 ko mice however display migration defects, while Lmnb2 ko mice do not have reduced size at birth. Heterozygous Lmnb1 mice do not present microcephaly. It is suggested that while animal models support a similar (to the human) phenotype the underlying mechanism is different.

Variant effect :
variants were shown to affect highly conserved residues within the lamin a-helical rod-domain. As affected residues are conserved in LMNA, modelling with available LMNA PDB structures, suggested disrupted interactions required for higher-order assembly of lamin filaments.

Recurrence of specific variants at specific residues, absence of pLoF ones, the htz mouse Lmnb1 phenotype (absence of microcephaly) and the proposed mechanism (perturbation of complex formation) suggest a gain-of-function/dominant-negative effect rather than happloinsufficiency.

[Please also note the additional OMIM phenotypes for LMNB1 / LMNB2 - not here reviewed]

--------
Intellectual disability syndromic and non-syndromic v0.3078 MICU1 Zornitza Stark Marked gene: MICU1 as ready
Intellectual disability syndromic and non-syndromic v0.3078 MICU1 Zornitza Stark Gene: micu1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3078 MICU1 Zornitza Stark Phenotypes for gene: MICU1 were changed from to Myopathy with extrapyramidal signs, MIM# 615673
Intellectual disability syndromic and non-syndromic v0.3077 MICU1 Zornitza Stark Publications for gene: MICU1 were set to
Intellectual disability syndromic and non-syndromic v0.3076 MICU1 Zornitza Stark Mode of inheritance for gene: MICU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3075 MICU1 Zornitza Stark Tag founder tag was added to gene: MICU1.
Intellectual disability syndromic and non-syndromic v0.3075 MICU1 Zornitza Stark reviewed gene: MICU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24336167, 29721912, 32395406; Phenotypes: Myopathy with extrapyramidal signs, MIM# 615673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3075 PIBF1 Zornitza Stark Phenotypes for gene: PIBF1 were changed from Joubert syndrome 33; OMIM #617767 to Joubert syndrome 33, OMIM #617767
Intellectual disability syndromic and non-syndromic v0.3074 PIBF1 Zornitza Stark Publications for gene: PIBF1 were set to PubMed: 26167768; 30858804; 29695797
Intellectual disability syndromic and non-syndromic v0.3073 PIBF1 Zornitza Stark reviewed gene: PIBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33004012; Phenotypes: Joubert syndrome 33, OMIM #617767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3073 WDPCP Zornitza Stark Publications for gene: WDPCP were set to
Intellectual disability syndromic and non-syndromic v0.3072 WDPCP Zornitza Stark Classified gene: WDPCP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3072 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3071 WDPCP Zornitza Stark edited their review of gene: WDPCP: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.3071 WDPCP Zornitza Stark changed review comment from: Two families reported; the first one with a BBS phenotype, and in the second one affected individual had polysyndactyly and tongue hamartomas, so phenotype consistent with OFD rather than BBS.; to: At least four families reported with ciliopathy phenotypes (BBS, OFD, syndromic retinopathy).
Intellectual disability syndromic and non-syndromic v0.3071 WDPCP Zornitza Stark edited their review of gene: WDPCP: Changed publications: 20671153, 25427950, 32055034, 29588463, 28289185
Intellectual disability syndromic and non-syndromic v0.3071 WDPCP Zornitza Stark Mode of inheritance for gene: WDPCP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3070 WDPCP Zornitza Stark Classified gene: WDPCP as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3070 WDPCP Zornitza Stark Gene: wdpcp has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3069 WDPCP Zornitza Stark reviewed gene: WDPCP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20671153, 25427950; Phenotypes: Bardet-Biedl syndrome 15, MIM# 615992, OFD, Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3069 TRAPPC9 Zornitza Stark Tag SV/CNV tag was added to gene: TRAPPC9.
Intellectual disability syndromic and non-syndromic v0.3069 TRAPPC9 Zornitza Stark Publications for gene: TRAPPC9 were set to 30853973
Intellectual disability syndromic and non-syndromic v0.3068 TRAPPC9 Zornitza Stark reviewed gene: TRAPPC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 22549410, 20004765, 20004763, 30853973, 29187737; Phenotypes: Mental retardation, autosomal recessive 13, MIM# 613192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3068 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from Vici syndrome, MIM# 242840 to Vici syndrome, MIM# 242840
Intellectual disability syndromic and non-syndromic v0.3068 EPG5 Zornitza Stark Marked gene: EPG5 as ready
Intellectual disability syndromic and non-syndromic v0.3068 EPG5 Zornitza Stark Gene: epg5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3068 EPG5 Zornitza Stark Phenotypes for gene: EPG5 were changed from to Vici syndrome, MIM# 242840
Intellectual disability syndromic and non-syndromic v0.3067 EPG5 Zornitza Stark Publications for gene: EPG5 were set to
Intellectual disability syndromic and non-syndromic v0.3066 EPG5 Zornitza Stark Mode of inheritance for gene: EPG5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3065 EPG5 Zornitza Stark reviewed gene: EPG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23222957, 26917586; Phenotypes: Vici syndrome, MIM# 242840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3065 KIRREL3 Zornitza Stark Tag refuted tag was added to gene: KIRREL3.
Intellectual disability syndromic and non-syndromic v0.3065 HK1 Zornitza Stark Phenotypes for gene: HK1 were changed from to Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547
Intellectual disability syndromic and non-syndromic v0.3064 HK1 Zornitza Stark reviewed gene: HK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with visual defects and brain anomalies, MIM# 618547; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Marked gene: ITFG2 as ready
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Added comment: Comment when marking as ready: Agree with Amber rating, considering reported as part of heterogenous cohort reporting diagnostic outcomes and multiple candidate genes.
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Gene: itfg2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Classified gene: ITFG2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3064 ITFG2 Zornitza Stark Gene: itfg2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3063 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Intellectual disability syndromic and non-syndromic v0.3063 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3063 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3063 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3062 ITFG2 Konstantinos Varvagiannis gene: ITFG2 was added
gene: ITFG2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ITFG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITFG2 were set to 28397838; https://doi.org/10.1038/s41525-020-00150-z
Phenotypes for gene: ITFG2 were set to Neurodevelopmental abnormality; Intellectual disability; Developmental regression; Ataxia
Penetrance for gene: ITFG2 were set to Complete
Review for gene: ITFG2 was set to AMBER
Added comment: ITFG2 was suggested to be a candidate gene for autosomal recessive ID in the study by Harripaul et al (2018 - PMID: 28397838). The authors performed microarray and exome sequencing in 192 consanguineous families and identified a homozygous ITGF2 stopgain variant (NM_018463.3:c.472G>T / p.Glu158*) along with 3 additional variants segregating with ID within an investigated family (PK51).

Cheema et al (2020 - https://doi.org/10.1038/s41525-020-00150-z) report briefly on a male, born to consanguineous parents presenting with NDD, seizures, regression and ataxia. There was a similarly affected female sibling. Evaluation of ROH revealed a homozygous ITFG2 nonsense variant [NM_018463.3:c.361C>T / p.(Gln121*)]. Families in this study were investigated by trio WES or WGS.

Evaluation of data of the same lab revealed 3 additional unrelated subjects with overlapping phenotypes, notably NDD and ataxia. These individuals were - each - homozygous for pLoF variants [NM_018463.3:c.848-1G>A; NM_018463.3:c.704dupC, p.(Ala236fs), NM_018463.3:c.1000_1001delAT, p.(Ile334fs)].

As discussed in OMIM, ITFG2 encodes a subunit of the KICSTOR protein complex, having a role in regulating nutrient sensing by MTOR complex-1 (Wolfson et al 2017 - PMID : 28199306).

Please consider inclusion in the ID panel with amber rating, pending further details.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3062 SHMT2 Konstantinos Varvagiannis gene: SHMT2 was added
gene: SHMT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Penetrance for gene: SHMT2 were set to Complete
Review for gene: SHMT2 was set to GREEN
Added comment: García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).

Overall this gene can be considered for inclusion with (probably) green rating in gene panels for ID, metabolic / mitochondrial disorders, cardiomyopathy, congenital microcephaly, corpus callosum anomalies, etc.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3062 VPS41 Zornitza Stark Marked gene: VPS41 as ready
Intellectual disability syndromic and non-syndromic v0.3062 VPS41 Zornitza Stark Gene: vps41 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3062 VPS41 Zornitza Stark gene: VPS41 was added
gene: VPS41 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32808683
Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability
Review for gene: VPS41 was set to RED
Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3061 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031 to Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036
Intellectual disability syndromic and non-syndromic v0.3060 ALG14 Zornitza Stark edited their review of gene: ALG14: Changed phenotypes: intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031, Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036
Intellectual disability syndromic and non-syndromic v0.3060 QRICH1 Zornitza Stark Marked gene: QRICH1 as ready
Intellectual disability syndromic and non-syndromic v0.3060 QRICH1 Zornitza Stark Gene: qrich1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3060 QRICH1 Zornitza Stark Phenotypes for gene: QRICH1 were changed from to Ververi-Brady syndrome, MIM#617982
Intellectual disability syndromic and non-syndromic v0.3059 QRICH1 Zornitza Stark Publications for gene: QRICH1 were set to
Intellectual disability syndromic and non-syndromic v0.3058 QRICH1 Zornitza Stark Mode of inheritance for gene: QRICH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3057 QRICH1 Zornitza Stark reviewed gene: QRICH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28692176, 30281152, 33009816; Phenotypes: Ververi-Brady syndrome, MIM#617982; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3057 SON Zornitza Stark Marked gene: SON as ready
Intellectual disability syndromic and non-syndromic v0.3057 SON Zornitza Stark Gene: son has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3057 SON Zornitza Stark Phenotypes for gene: SON were changed from to ZTTK syndrome, MIM# 617140
Intellectual disability syndromic and non-syndromic v0.3056 SON Zornitza Stark Publications for gene: SON were set to
Intellectual disability syndromic and non-syndromic v0.3055 SON Zornitza Stark Mode of inheritance for gene: SON was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3054 SON Zornitza Stark reviewed gene: SON: Rating: GREEN; Mode of pathogenicity: None; Publications: 27545680, 27545676, 31005274; Phenotypes: ZTTK syndrome, MIM# 617140; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3054 NEMF Zornitza Stark Mode of inheritance for gene: NEMF was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Zornitza Stark edited their review of gene: NEMF: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Konstantinos Varvagiannis changed review comment from: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).; to: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides produced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration in mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Konstantinos Varvagiannis changed review comment from: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variants were on the same allele, as phase was not been determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).; to: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variant were on the same allele, as phase was not determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Konstantinos Varvagiannis changed review comment from: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could be ruled out that the de novo and maternally inherited variants were on the same allele, as phase was not been determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).; to: Biallelic (and possibly monoallelic) pathogenic variants in this gene are associated with DD/ID.

Martin et al (2020 - PMID:32934225) report on 8 individuals from 6 families with a juvenile neuromuscular disease due to biallelic NEMF variants. (In one of these 8 cases it could not be ruled out that a de novo and maternally inherited variants were on the same allele, as phase was not been determined). A ninth individual with similar presentation was found to harbor a single NEMF missense SNV as de novo event (due to a speculated dominant-negative effect). This individual had a similar presentation.

Features incl. hypotonia (4/8 with biallelic variant (B) | 1/1 monoallelic (M) ), DD/ID (7/8B | 0/1M) with speech delay as universal feature (8/8B | 1/1M), axonal neuropathy (3/3B | 1/1M), ataxia (3/8B | 0/1M). Other findings included tremor (1/7B | 1/1M), abnormal brain imaging (2/6B / ?/1M), kyphosis/scoliosis (4/8B | 0/1M), respiratory distress (1/8B | 0/1M).

NEMF (Rqc2 in yeast) encodes the nuclear export mediator factor, a component of the Ribosome-associated Quality Control (RCQ) complex which is involved in proteolytic targeting of incomplete polypeptides prodduced by ribosome stalling. NEMF facilitates the recruitment of E3 ligase Listerin (LTN1) which ubiquitinates nascent polypeptide chains for subsequent proteasomal degradation.

The author provide evidence that mice homozygous for Nemf missense mutations display progressive motor phenotypes, exhibit neurogenic atrophy and progressive axonal degeneration. A further NEMF-null mouse model displayed more severe phenotype (with heterozygous mice being unaffected).

Equivalent mutations (of those in the above mouse model) in yeast (Rqc2) were shown to interfere with its ability to modify aberrant translation products with C-terminal tails which assist RQC-mediated protein degradation.

Mutation of Ltn1 (belonging to the same protein control pathway) has been also shown to lead to neurodegeneration im mice.

Overall NEMF is thought to play a role in neuronal translational homeostasis and the disorder to be mediated by dysfunction of the RQC pathway (normally protecting neurons against degeneration).
Intellectual disability syndromic and non-syndromic v0.3053 NEMF Konstantinos Varvagiannis reviewed gene: NEMF: Rating: GREEN; Mode of pathogenicity: None; Publications: 32934225; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3053 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804; microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Intellectual disability syndromic and non-syndromic v0.3052 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed phenotypes: Sandestig-Stefanova syndrome, 618804, microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Intellectual disability syndromic and non-syndromic v0.3052 SETD1A Zornitza Stark Marked gene: SETD1A as ready
Intellectual disability syndromic and non-syndromic v0.3052 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3052 SETD1A Zornitza Stark Classified gene: SETD1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3052 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3051 SETD1A Zornitza Stark gene: SETD1A was added
gene: SETD1A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1A were set to 31197650; 32346159
Phenotypes for gene: SETD1A were set to Epilepsy, early-onset, with or without developmental delay, MIM# 618832
Review for gene: SETD1A was set to GREEN
Added comment: 19 unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype, primarily manifesting and ID and seizures. LOF mechanism supported by functional data. Three mouse models.

SNPs in this gene have also been associated with risk of developing schizophrenia.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3050 HPDL Zornitza Stark changed review comment from: Intellectual impairment is variable, ranging from poor visual contact with inability to walk or speak to milder intellectual disability with the ability to say some words.; to: 17 individuals from 13 families, with a spectrum of neurologic impairment ranging from a severe congenital form without any neurological development (n = 2/17, 12%) to infantile-onset presentations (n = 10/17, 59%) with moderate to severe neurodevelopmental issues, partly with a pathology reminiscent of mitochondrial disease (Leigh-like syndrome), to juvenile-onset spastic paraplegia (n = 5/17, 29%).

Intellectual impairment is variable, ranging from poor visual contact with inability to walk or speak to milder intellectual disability with the ability to say some words.

Frequently observed additional clinical findings included chronic progression of neurological signs (n = 16/17, 94%), microcephaly (n = 9/16, 56%), and seizures/epilepsy (n = 9/17, 53%). Other relevant clinical findings were visual disturbances/strabismus (n = 9/17, 53%) and loss of developmental milestones (n = 6/17, 35%).

Acute central respiratory failure leading to life-threatening events requiring partly mechanically assisted ventilation occurred in half of individuals with infantile presentation (n = 5/10, 50%), respectively one third of all individuals (n = 5/17, 29%).

Demyelinating neuropathy was present in three individuals (n = 3/11, 27%), with reduced sensory nerve conduction velocity (NCV) in all and severely reduced motor NCV in one.
Intellectual disability syndromic and non-syndromic v0.3050 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Progressive neurological disorder; Leigh-like syndrome to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Progressive neurological disorder; Leigh-like syndrome
Intellectual disability syndromic and non-syndromic v0.3049 HPDL Zornitza Stark reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), MIM#619026; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.3049 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Intellectual disability syndromic and non-syndromic v0.3049 PRKD1 Zornitza Stark Added comment: Comment when marking as ready: Literature reviewed again: ID/DD reported in 2/5 but unclear at present if this is part of the phenotype given low number of affected individuals.
Intellectual disability syndromic and non-syndromic v0.3049 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3049 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to 27479907
Intellectual disability syndromic and non-syndromic v0.3048 PRKD1 Zornitza Stark Classified gene: PRKD1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3048 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3047 PRKD1 Arina Puzriakova reviewed gene: PRKD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27479907, 32817298; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.3047 KPTN Zornitza Stark Marked gene: KPTN as ready
Intellectual disability syndromic and non-syndromic v0.3047 KPTN Zornitza Stark Gene: kptn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3047 KPTN Zornitza Stark Phenotypes for gene: KPTN were changed from to Mental retardation, autosomal recessive 41 (MIM#615637)
Intellectual disability syndromic and non-syndromic v0.3046 KPTN Zornitza Stark Publications for gene: KPTN were set to
Intellectual disability syndromic and non-syndromic v0.3045 KPTN Zornitza Stark Mode of inheritance for gene: KPTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3044 KPTN Zornitza Stark reviewed gene: KPTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24239382, 32358097, 32808430; Phenotypes: Mental retardation, autosomal recessive 41 (MIM#615637); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3044 TTI2 Zornitza Stark Marked gene: TTI2 as ready
Intellectual disability syndromic and non-syndromic v0.3044 TTI2 Zornitza Stark Gene: tti2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3044 TTI2 Zornitza Stark Phenotypes for gene: TTI2 were changed from to Mental retardation, autosomal recessive 39 (MIM#615541) AR
Intellectual disability syndromic and non-syndromic v0.3043 TTI2 Zornitza Stark Publications for gene: TTI2 were set to
Intellectual disability syndromic and non-syndromic v0.3042 TTI2 Zornitza Stark Mode of inheritance for gene: TTI2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3041 TTI2 Michelle Torres reviewed gene: TTI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32061250, 23956177, 31737043; Phenotypes: Mental retardation, autosomal recessive 39 (MIM#615541) AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3041 ARID2 Zornitza Stark reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26238514, 30838730, 29698805, 28884947, 28124119; Phenotypes: Coffin-Siris syndrome 6, MIM# 617808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3041 ARID2 Zornitza Stark Marked gene: ARID2 as ready
Intellectual disability syndromic and non-syndromic v0.3041 ARID2 Zornitza Stark Gene: arid2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3041 ARID2 Zornitza Stark Phenotypes for gene: ARID2 were changed from to Coffin-Siris syndrome 6, MIM# 617808
Intellectual disability syndromic and non-syndromic v0.3040 ARID2 Zornitza Stark Publications for gene: ARID2 were set to
Intellectual disability syndromic and non-syndromic v0.3039 ARID2 Zornitza Stark Mode of inheritance for gene: ARID2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3038 ARID2 Ee Ming Wong reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26238514; Phenotypes: neurodevelopmental delay, global developmental delay, gross motor delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.3038 PIGT Zornitza Stark Marked gene: PIGT as ready
Intellectual disability syndromic and non-syndromic v0.3038 PIGT Zornitza Stark Gene: pigt has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3038 PIGT Zornitza Stark Phenotypes for gene: PIGT were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398
Intellectual disability syndromic and non-syndromic v0.3037 PIGT Zornitza Stark Publications for gene: PIGT were set to
Intellectual disability syndromic and non-syndromic v0.3036 PIGT Zornitza Stark Mode of inheritance for gene: PIGT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3035 PIGT Zornitza Stark reviewed gene: PIGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 30976099, 25943031, 24906948, 24906948, 24906948, 28728837, 28728837, 28728837; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 3, MIM# 615398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3035 ALG13 Zornitza Stark Marked gene: ALG13 as ready
Intellectual disability syndromic and non-syndromic v0.3035 ALG13 Zornitza Stark Gene: alg13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3035 ALG13 Zornitza Stark Phenotypes for gene: ALG13 were changed from to Congenital disorder of glycosylation, type Is (MIM# 300884)
Intellectual disability syndromic and non-syndromic v0.3034 ALG13 Zornitza Stark Publications for gene: ALG13 were set to
Intellectual disability syndromic and non-syndromic v0.3033 ALG13 Zornitza Stark Mode of inheritance for gene: ALG13 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.3032 ALG13 Zornitza Stark reviewed gene: ALG13: Rating: GREEN; Mode of pathogenicity: None; Publications: 23033978, 23934111, 24781210, 24896178, 25732998, 26138355, 26482601, 28940310, 32238909; Phenotypes: Congenital disorder of glycosylation, type Is (MIM# 300884); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.3032 GPSM2 Zornitza Stark edited their review of gene: GPSM2: Changed publications: 20602914, 22578326, 28387217, 27180139, 27064331
Intellectual disability syndromic and non-syndromic v0.3032 GPSM2 Zornitza Stark Publications for gene: GPSM2 were set to
Intellectual disability syndromic and non-syndromic v0.3031 GPSM2 Zornitza Stark Mode of inheritance for gene: GPSM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3030 CNOT1 Zornitza Stark Phenotypes for gene: CNOT1 were changed from Holoprosencephaly 12, with or without pancreatic agenesis 618500 to Vissers-Bodmer syndrome, MIM#619033; Holoprosencephaly 12, with or without pancreatic agenesis 618500
Intellectual disability syndromic and non-syndromic v0.3029 CNOT1 Zornitza Stark Publications for gene: CNOT1 were set to 31006510; 21679367; 31006513
Intellectual disability syndromic and non-syndromic v0.3028 CNOT1 Zornitza Stark reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vissers-Bodmer syndrome, MIM#619033; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3028 COQ5 Zornitza Stark Phenotypes for gene: COQ5 were changed from Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability to Coenzyme Q10 deficiency, primary 9, MIM#619028; Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability
Intellectual disability syndromic and non-syndromic v0.3027 COQ5 Zornitza Stark edited their review of gene: COQ5: Changed phenotypes: Coenzyme Q10 deficiency, primary 9, MIM#619028, Cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, intellectual disability
Intellectual disability syndromic and non-syndromic v0.3027 SECISBP2 Zornitza Stark Marked gene: SECISBP2 as ready
Intellectual disability syndromic and non-syndromic v0.3027 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3027 SECISBP2 Zornitza Stark Classified gene: SECISBP2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.3027 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.3026 SECISBP2 Anna Le Fevre gene: SECISBP2 was added
gene: SECISBP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SECISBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SECISBP2 were set to 16228000; 19602558; 21084748; 22247018
Phenotypes for gene: SECISBP2 were set to #609698 THYROID HORMONE METABOLISM, ABNORMAL
Penetrance for gene: SECISBP2 were set to unknown
Review for gene: SECISBP2 was set to RED
Added comment: Multiple families with biallelic loss of function variants have been reported with a disorder of thyroid hormone metabolism involving synthesis of selenoproteins. Features include short stature with delayed bone age, muscle weakness with fatty infiltration of skeletal muscle, azoospermia, and mild developmental delay. Photosensitivity and high frequency SNHL have been reported. Thyroid function tests show elevated FT4 and rT3, low FT3 and normal or mildly elevated TSH. Incomplete loss of SECISBP2 function has been hypothesized to cause a milder phenotype.

At least two reports of children with delayed milestones.
One report of an affected adult with mild ID.
Further reports may clarify if this phenotype typically includes ID.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3026 LAS1L Zornitza Stark Mode of inheritance for gene: LAS1L was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3025 LAS1L Zornitza Stark edited their review of gene: LAS1L: Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3025 UPF3B Zornitza Stark Marked gene: UPF3B as ready
Intellectual disability syndromic and non-syndromic v0.3025 UPF3B Zornitza Stark Gene: upf3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3025 UPF3B Zornitza Stark Phenotypes for gene: UPF3B were changed from to Mental retardation, X-linked, syndromic 14, MIM# 300676
Intellectual disability syndromic and non-syndromic v0.3024 UPF3B Zornitza Stark Publications for gene: UPF3B were set to
Intellectual disability syndromic and non-syndromic v0.3023 UPF3B Zornitza Stark Mode of inheritance for gene: UPF3B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3022 UPF3B Zornitza Stark reviewed gene: UPF3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19377476, 17704778, 31737052, 28948974; Phenotypes: Mental retardation, X-linked, syndromic 14, MIM# 300676; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3022 UPF3B Arina Puzriakova reviewed gene: UPF3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32667670; Phenotypes: Mental retardation, X-linked, syndromic 14, 300676; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.3022 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from Myasthenic syndrome, congenital, 15, without tubular aggregates, MIM#616227; Intellectual disability to Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031
Intellectual disability syndromic and non-syndromic v0.3021 ALG14 Zornitza Stark edited their review of gene: ALG14: Changed phenotypes: intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031
Intellectual disability syndromic and non-syndromic v0.3021 MADD Zornitza Stark Phenotypes for gene: MADD were changed from intellectual disability to DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities); Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005
Intellectual disability syndromic and non-syndromic v0.3020 MADD Zornitza Stark Publications for gene: MADD were set to 28940097
Intellectual disability syndromic and non-syndromic v0.3019 MADD Zornitza Stark reviewed gene: MADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 29302074, 32761064; Phenotypes: DEEAH syndrome, MIM#619004 (Developmental Delay With Endocrine, Exocrine, Autonomic, and Hematologic Abnormalities), Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (NEDDISH), MIM# 619005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3019 SLC12A2 Zornitza Stark Publications for gene: SLC12A2 were set to 30740830
Intellectual disability syndromic and non-syndromic v0.3018 SLC12A2 Zornitza Stark Mode of inheritance for gene: SLC12A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3017 SLC12A2 Konstantinos Varvagiannis reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28135719, 32658972, 27900370, 32294086, 29288388, 30740830, 32754646; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3017 TECPR2 Zornitza Stark Marked gene: TECPR2 as ready
Intellectual disability syndromic and non-syndromic v0.3017 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3017 TECPR2 Zornitza Stark Phenotypes for gene: TECPR2 were changed from to Spastic paraplegia 49, autosomal recessive, 615031; Autonomic-sensory neuropathy; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.3016 TECPR2 Zornitza Stark Publications for gene: TECPR2 were set to
Intellectual disability syndromic and non-syndromic v0.3015 TECPR2 Zornitza Stark Mode of inheritance for gene: TECPR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3014 TECPR2 Zornitza Stark reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176824, 26542466; Phenotypes: Spastic paraplegia 49, autosomal recessive, 615031, Autonomic-sensory neuropathy, Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark edited their review of gene: ZMYM2: Changed rating: GREEN; Changed publications: 32891193; Changed phenotypes: Congenital anomalies of kidney and urinary tract, Neurodevelopmental disorder; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Marked gene: ZMYM2 as ready
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Added comment: Comment when marking as ready: Syndromic CAKUT, variable extra-renal phenotype but sufficient families with ID for Green rating.
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Classified gene: ZMYM2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3014 ZMYM2 Zornitza Stark Gene: zmym2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3013 ZMYM2 Konstantinos Varvagiannis gene: ZMYM2 was added
gene: ZMYM2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZMYM2 were set to 32891193
Phenotypes for gene: ZMYM2 were set to Abnormality of the urinary system; Global developmental delay; Intellectual disability; Microcephaly; Abnormality of the cardiovascular system; Autism; Seizures; Abnormality of the head or neck; Abnormality of the nail; Small hand; Short foot; Clinodactyly
Penetrance for gene: ZMYM2 were set to unknown
Review for gene: ZMYM2 was set to AMBER
Added comment: Heterozygous pathogenic (pLoF) ZMYM2 variants have been reported in individuals with syndromic presentation including CAKUT (in several cases) and variable neurological manifestations among extra-renal features. DD and ID were reported in some of the families described to date as summarized below. You might consider inclusion with green/amber rating in the ID panel and green in the panel for CAKUT.

--

Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants. [Article not reviewed in detail].

Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly.

14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family.

The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT.

ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body).

It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors.

The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3013 NEMF Zornitza Stark Marked gene: NEMF as ready
Intellectual disability syndromic and non-syndromic v0.3013 NEMF Zornitza Stark Gene: nemf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3013 NEMF Zornitza Stark Classified gene: NEMF as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3013 NEMF Zornitza Stark Gene: nemf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3012 NEMF Zornitza Stark gene: NEMF was added
gene: NEMF was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NEMF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEMF were set to 32934225
Phenotypes for gene: NEMF were set to Intellectual disability; neuropathy
Review for gene: NEMF was set to GREEN
Added comment: Nine individuals from 7 unrelated families reported with a mixed CNS/PNS phenotype. 7/9 had ID, 4/9 had formal assessments demonstrating axonal neuropathy, 3/9 had ataxia; muscular atrophy, hypotonia, respiratory distress, scoliosis also described in some. Three independently generated mouse models had progressive motor neuron degeneration.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3011 LMNB1 Zornitza Stark Marked gene: LMNB1 as ready
Intellectual disability syndromic and non-syndromic v0.3011 LMNB1 Zornitza Stark Added comment: Comment when marking as ready: Note different mechanism for LMNB1-related neurodevelopmental phenotype cf Adult-onset leukodystrophy phenotype previously associated with this gene.
Intellectual disability syndromic and non-syndromic v0.3011 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3011 LMNB1 Zornitza Stark Phenotypes for gene: LMNB1 were changed from Leukodystrophy, adult-onset, autosomal dominant, MIM#169500 to Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Leukodystrophy, adult-onset, autosomal dominant, MIM#169500
Intellectual disability syndromic and non-syndromic v0.3010 LMNB1 Zornitza Stark Publications for gene: LMNB1 were set to
Intellectual disability syndromic and non-syndromic v0.3009 LMNB1 Zornitza Stark Mode of pathogenicity for gene: LMNB1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.3008 LMNB1 Zornitza Stark Classified gene: LMNB1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.3008 LMNB1 Zornitza Stark Gene: lmnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3007 LMNB1 Konstantinos Varvagiannis edited their review of gene: LMNB1: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.3007 LMNB1 Konstantinos Varvagiannis edited their review of gene: LMNB1: Changed mode of pathogenicity: Other
Intellectual disability syndromic and non-syndromic v0.3007 LMNB1 Konstantinos Varvagiannis reviewed gene: LMNB1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 32910914; Phenotypes: Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.3007 VPS11 Zornitza Stark Tag founder tag was added to gene: VPS11.
Intellectual disability syndromic and non-syndromic v0.3007 SVBP Zornitza Stark Tag founder tag was added to gene: SVBP.
Intellectual disability syndromic and non-syndromic v0.3007 SVBP Zornitza Stark reviewed gene: SVBP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, OMIM #618569; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.3007 MAPK8IP3 Zornitza Stark Publications for gene: MAPK8IP3 were set to 30612693
Intellectual disability syndromic and non-syndromic v0.3006 MAPK8IP3 Zornitza Stark reviewed gene: MAPK8IP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30612693, 30945334; Phenotypes: Neurodevelopmental disorder with or without variable brain abnormalities, MIM# 618443; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3006 KCNA2 Zornitza Stark Marked gene: KCNA2 as ready
Intellectual disability syndromic and non-syndromic v0.3006 KCNA2 Zornitza Stark Gene: kcna2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3006 KCNA2 Zornitza Stark Phenotypes for gene: KCNA2 were changed from to Early infantile encephalopathy 32, MIM#616366
Intellectual disability syndromic and non-syndromic v0.3005 KCNA2 Zornitza Stark Publications for gene: KCNA2 were set to
Intellectual disability syndromic and non-syndromic v0.3004 KCNA2 Zornitza Stark Mode of inheritance for gene: KCNA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3003 KCNA2 Zornitza Stark reviewed gene: KCNA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29050392; Phenotypes: Early infantile encephalopathy 32, MIM#616366; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3003 EBF3 Zornitza Stark Marked gene: EBF3 as ready
Intellectual disability syndromic and non-syndromic v0.3003 EBF3 Zornitza Stark Gene: ebf3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3003 EBF3 Zornitza Stark Phenotypes for gene: EBF3 were changed from to Hypotonia, ataxia, and delayed development syndrome, MIM# 617330
Intellectual disability syndromic and non-syndromic v0.3002 EBF3 Zornitza Stark Publications for gene: EBF3 were set to
Intellectual disability syndromic and non-syndromic v0.3001 EBF3 Zornitza Stark Mode of inheritance for gene: EBF3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3000 EBF3 Zornitza Stark reviewed gene: EBF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28017373, 28017372, 28017370, 32366537; Phenotypes: Hypotonia, ataxia, and delayed development syndrome, MIM# 617330; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.3000 DOCK3 Zornitza Stark Marked gene: DOCK3 as ready
Intellectual disability syndromic and non-syndromic v0.3000 DOCK3 Zornitza Stark Gene: dock3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.3000 DOCK3 Zornitza Stark Phenotypes for gene: DOCK3 were changed from to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292
Intellectual disability syndromic and non-syndromic v0.2999 DOCK3 Zornitza Stark Publications for gene: DOCK3 were set to
Intellectual disability syndromic and non-syndromic v0.2998 DOCK3 Zornitza Stark Mode of inheritance for gene: DOCK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2997 DOCK3 Zornitza Stark reviewed gene: DOCK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28195318, 29130632, 30976111; Phenotypes: Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2997 ALDH5A1 Zornitza Stark Marked gene: ALDH5A1 as ready
Intellectual disability syndromic and non-syndromic v0.2997 ALDH5A1 Zornitza Stark Gene: aldh5a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2997 ALDH5A1 Zornitza Stark Phenotypes for gene: ALDH5A1 were changed from to Succinic semialdehyde dehydrogenase deficiency, MIM# 271980
Intellectual disability syndromic and non-syndromic v0.2996 ALDH5A1 Zornitza Stark Publications for gene: ALDH5A1 were set to
Intellectual disability syndromic and non-syndromic v0.2995 ALDH5A1 Zornitza Stark Mode of inheritance for gene: ALDH5A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2994 ALDH5A1 Zornitza Stark reviewed gene: ALDH5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14635103; Phenotypes: Succinic semialdehyde dehydrogenase deficiency, MIM# 271980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2994 SPRED1 Zornitza Stark Marked gene: SPRED1 as ready
Intellectual disability syndromic and non-syndromic v0.2994 SPRED1 Zornitza Stark Gene: spred1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2994 SPRED1 Zornitza Stark Phenotypes for gene: SPRED1 were changed from to Legius syndrome, MIM# 611431
Intellectual disability syndromic and non-syndromic v0.2993 SPRED1 Zornitza Stark Publications for gene: SPRED1 were set to
Intellectual disability syndromic and non-syndromic v0.2992 SPRED1 Zornitza Stark Mode of inheritance for gene: SPRED1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2991 SPRED1 Zornitza Stark reviewed gene: SPRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17704776, 19366998, 21548021; Phenotypes: Legius syndrome, MIM# 611431; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2991 SOS1 Zornitza Stark Marked gene: SOS1 as ready
Intellectual disability syndromic and non-syndromic v0.2991 SOS1 Zornitza Stark Gene: sos1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2991 SOS1 Zornitza Stark Phenotypes for gene: SOS1 were changed from to Noonan syndrome 4, MIM# 610733
Intellectual disability syndromic and non-syndromic v0.2990 SOS1 Zornitza Stark Publications for gene: SOS1 were set to
Intellectual disability syndromic and non-syndromic v0.2989 SOS1 Zornitza Stark Mode of pathogenicity for gene: SOS1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.2988 SOS1 Zornitza Stark Mode of inheritance for gene: SOS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2987 SOS1 Zornitza Stark reviewed gene: SOS1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 17143285, 17143282, 28884940, 17586837; Phenotypes: Noonan syndrome 4, MIM# 610733; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2987 HRAS Zornitza Stark Marked gene: HRAS as ready
Intellectual disability syndromic and non-syndromic v0.2987 HRAS Zornitza Stark Gene: hras has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2987 HRAS Zornitza Stark Phenotypes for gene: HRAS were changed from to Costello syndrome, MIM# 218040
Intellectual disability syndromic and non-syndromic v0.2986 HRAS Zornitza Stark Publications for gene: HRAS were set to
Intellectual disability syndromic and non-syndromic v0.2985 HRAS Zornitza Stark Mode of pathogenicity for gene: HRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.2984 HRAS Zornitza Stark Mode of inheritance for gene: HRAS was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2983 HRAS Zornitza Stark reviewed gene: HRAS: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 16329078, 16372351, 16443854; Phenotypes: Costello syndrome, MIM# 218040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2983 VAMP2 Zornitza Stark Phenotypes for gene: VAMP2 were changed from Intellectual disability; autism; no OMIM number yet to Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements 618760; Cortical visual impairment; Seizures; Stereotypic behaviour; Generalized hypotonia; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.2982 VAMP2 Zornitza Stark reviewed gene: VAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements 618760, Cortical visual impairment, Seizures, Stereotypic behaviour, Generalized hypotonia, Intellectual disability; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2982 SLC16A2 Zornitza Stark changed review comment from: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability.; to: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. In a recent review of 24 affected individuals (PMID 31410843), 16 presented with profound developmental delay, three had severe intellectual disability with poor language and walking with an aid, four had moderate intellectual disability with language and walking abilities, and one had mild intellectual disability with hypotonia. Overall, eight had learned to walk, all had hypotonia, 17 had spasticity, 18 had dystonia, 12 had choreoathetosis, 19 had hypomyelination, and 10 had brain atrophy. Kyphoscoliosis (n=12), seizures (n=7), and pneumopathies (n=5) were the most severe complications.
Intellectual disability syndromic and non-syndromic v0.2982 SLC16A2 Zornitza Stark Marked gene: SLC16A2 as ready
Intellectual disability syndromic and non-syndromic v0.2982 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2982 SLC16A2 Zornitza Stark Phenotypes for gene: SLC16A2 were changed from to Allan-Herndon-Dudley syndrome, MIM# 300523
Intellectual disability syndromic and non-syndromic v0.2981 SLC16A2 Zornitza Stark Publications for gene: SLC16A2 were set to
Intellectual disability syndromic and non-syndromic v0.2980 SLC16A2 Zornitza Stark Mode of inheritance for gene: SLC16A2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2979 SLC16A2 Zornitza Stark reviewed gene: SLC16A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15980113, 31410843, 20301789; Phenotypes: Allan-Herndon-Dudley syndrome, MIM# 300523; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2979 HECW2 Zornitza Stark Marked gene: HECW2 as ready
Intellectual disability syndromic and non-syndromic v0.2979 HECW2 Zornitza Stark Gene: hecw2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2979 HECW2 Zornitza Stark Phenotypes for gene: HECW2 were changed from to Neurodevelopmental disorder with hypotonia, seizures, and absent language (MIM#617268)
Intellectual disability syndromic and non-syndromic v0.2978 HECW2 Zornitza Stark Publications for gene: HECW2 were set to
Intellectual disability syndromic and non-syndromic v0.2977 HECW2 Zornitza Stark Mode of inheritance for gene: HECW2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2976 HECW2 Teresa Zhao reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27389779; Phenotypes: Neurodevelopmental disorder with hypotonia, seizures, and absent language (MIM#617268); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2976 NR2F1 Zornitza Stark Marked gene: NR2F1 as ready
Intellectual disability syndromic and non-syndromic v0.2976 NR2F1 Zornitza Stark Gene: nr2f1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2976 NR2F1 Zornitza Stark Phenotypes for gene: NR2F1 were changed from to Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM# 615722
Intellectual disability syndromic and non-syndromic v0.2975 NR2F1 Zornitza Stark Publications for gene: NR2F1 were set to
Intellectual disability syndromic and non-syndromic v0.2974 NR2F1 Zornitza Stark Mode of inheritance for gene: NR2F1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2973 NR2F1 Zornitza Stark reviewed gene: NR2F1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32275123; Phenotypes: Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM# 615722; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2973 HSPA9 Zornitza Stark Marked gene: HSPA9 as ready
Intellectual disability syndromic and non-syndromic v0.2973 HSPA9 Zornitza Stark Gene: hspa9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2973 HSPA9 Zornitza Stark Phenotypes for gene: HSPA9 were changed from OMIM 616854; skeletal anomalies; congenital cardiac and renal anom to Even-plus syndrome, OMIM 616854; skeletal anomalies; congenital cardiac and renal anom
Intellectual disability syndromic and non-syndromic v0.2972 HSPA9 Sue White Classified gene: HSPA9 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2972 HSPA9 Sue White Gene: hspa9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2971 HSPA9 Sue White commented on gene: HSPA9: 2 patients with dev delay in 5 published patients with Even-plus syndrome
Intellectual disability syndromic and non-syndromic v0.2971 HSPA9 Sue White gene: HSPA9 was added
gene: HSPA9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HSPA9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSPA9 were set to 32869452; 26598328
Phenotypes for gene: HSPA9 were set to OMIM 616854; skeletal anomalies; congenital cardiac and renal anom
Penetrance for gene: HSPA9 were set to Complete
Review for gene: HSPA9 was set to AMBER
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2970 WASHC4 Zornitza Stark reviewed gene: WASHC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2970 WASHC4 Alison Yeung Classified gene: WASHC4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2970 WASHC4 Alison Yeung Gene: washc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2969 WASHC4 Alison Yeung Deleted their comment
Intellectual disability syndromic and non-syndromic v0.2969 WASHC4 Alison Yeung reviewed gene: WASHC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31953988; Phenotypes: Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2969 ATP1A3 Seb Lunke Classified gene: ATP1A3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2969 ATP1A3 Seb Lunke Gene: atp1a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2968 ATP1A3 Seb Lunke reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2968 MYT1L Zornitza Stark Tag SV/CNV tag was added to gene: MYT1L.
Intellectual disability syndromic and non-syndromic v0.2968 MYT1L Zornitza Stark Publications for gene: MYT1L were set to 28859103
Intellectual disability syndromic and non-syndromic v0.2967 MYT1L Zornitza Stark reviewed gene: MYT1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 32065501; Phenotypes: Mental retardation, autosomal dominant 39, MIM# 616521; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2967 ARID1A Crystle Lee reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23929686, 22426308, 25168959; Phenotypes: Coffin-Siris syndrome 2 (MIM#614607); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2967 GTPBP2 Zornitza Stark Marked gene: GTPBP2 as ready
Intellectual disability syndromic and non-syndromic v0.2967 GTPBP2 Zornitza Stark Gene: gtpbp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2967 GTPBP2 Zornitza Stark Phenotypes for gene: GTPBP2 were changed from to Jaberi-Elahi syndrome, MIM#617988
Intellectual disability syndromic and non-syndromic v0.2966 GTPBP2 Zornitza Stark Publications for gene: GTPBP2 were set to
Intellectual disability syndromic and non-syndromic v0.2965 GTPBP2 Zornitza Stark Mode of inheritance for gene: GTPBP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2964 GTPBP2 Zornitza Stark reviewed gene: GTPBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26675814, 29449720, 30790272; Phenotypes: Jaberi-Elahi syndrome, MIM#617988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2964 GNB1 Zornitza Stark Marked gene: GNB1 as ready
Intellectual disability syndromic and non-syndromic v0.2964 GNB1 Zornitza Stark Gene: gnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2964 GNB1 Zornitza Stark Phenotypes for gene: GNB1 were changed from to Mental retardation, autosomal dominant 42, MIM# 616973
Intellectual disability syndromic and non-syndromic v0.2963 GNB1 Zornitza Stark Publications for gene: GNB1 were set to
Intellectual disability syndromic and non-syndromic v0.2962 GNB1 Zornitza Stark Mode of inheritance for gene: GNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2961 GNB1 Zornitza Stark reviewed gene: GNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27108799, 30194818, 27668284, 31034681; Phenotypes: Mental retardation, autosomal dominant 42, MIM# 616973; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2961 FITM2 Zornitza Stark Marked gene: FITM2 as ready
Intellectual disability syndromic and non-syndromic v0.2961 FITM2 Zornitza Stark Gene: fitm2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2961 FITM2 Zornitza Stark Classified gene: FITM2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2961 FITM2 Zornitza Stark Gene: fitm2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2960 FITM2 Zornitza Stark gene: FITM2 was added
gene: FITM2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635
Review for gene: FITM2 was set to GREEN
Added comment: Autosomal recessive condition characterised by global developmental delay, early-onset progressive sensorineural hearing impairment, regression of motor skills, dystonia, poor overall growth, and low body mass index (BMI). More variable features may include ichthyosis-like skin abnormalities or sensory neuropathy. 7 individuals from three unrelated families reported, supportive Drosophila model.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2959 FDXR Zornitza Stark Publications for gene: FDXR were set to
Intellectual disability syndromic and non-syndromic v0.2958 FDXR Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Bi-allelic variants in FDXR cause an autosomal recessive neurologic disorder characterised by onset of visual and hearing impairment in the first or second decades. Two individuals described with a more severe phenotype, including one with intellectual disability.
Intellectual disability syndromic and non-syndromic v0.2958 FDXR Zornitza Stark edited their review of gene: FDXR: Changed publications: 30250212
Intellectual disability syndromic and non-syndromic v0.2958 EIF2S3 Zornitza Stark Marked gene: EIF2S3 as ready
Intellectual disability syndromic and non-syndromic v0.2958 EIF2S3 Zornitza Stark Gene: eif2s3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2958 EIF2S3 Zornitza Stark Phenotypes for gene: EIF2S3 were changed from to MEHMO syndrome, MIM# 300148
Intellectual disability syndromic and non-syndromic v0.2957 EIF2S3 Zornitza Stark Publications for gene: EIF2S3 were set to
Intellectual disability syndromic and non-syndromic v0.2956 EIF2S3 Zornitza Stark Mode of inheritance for gene: EIF2S3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2955 EIF2S3 Zornitza Stark reviewed gene: EIF2S3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23063529, 27333055, 28055140, 32799315; Phenotypes: MEHMO syndrome, MIM# 300148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2955 SETD1B Zornitza Stark Phenotypes for gene: SETD1B were changed from SETD1B-related neurodevelopmental disorder to Intellectual developmental disorder with seizures and language delay (IDDSELD), MIM#619000
Intellectual disability syndromic and non-syndromic v0.2954 TRIP13 Zornitza Stark Tag founder tag was added to gene: TRIP13.
Intellectual disability syndromic and non-syndromic v0.2954 TRIP13 Zornitza Stark changed review comment from: Early-onset Wilms tumor and either aneuploidy or premature chromatid separation in cells. Some individuals described as having additional developmental features, such as microcephaly, growth retardation, or developmental delay but these are highly variable.; to: Early-onset Wilms tumor and either aneuploidy or premature chromatid separation in cells. Some individuals described as having additional developmental features, such as microcephaly, growth retardation, or developmental delay but these are highly variable. Also note 5/6 reported families had the same homozygous variant, p.Arg354X, suggestive of founder effect.
Intellectual disability syndromic and non-syndromic v0.2954 TRAPPC6B Zornitza Stark Marked gene: TRAPPC6B as ready
Intellectual disability syndromic and non-syndromic v0.2954 TRAPPC6B Zornitza Stark Gene: trappc6b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2954 TRAPPC6B Zornitza Stark Phenotypes for gene: TRAPPC6B were changed from to Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, MIM# 617862
Intellectual disability syndromic and non-syndromic v0.2953 TRAPPC6B Zornitza Stark Publications for gene: TRAPPC6B were set to
Intellectual disability syndromic and non-syndromic v0.2952 TRAPPC6B Zornitza Stark Mode of inheritance for gene: TRAPPC6B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2951 TRAPPC6B Zornitza Stark reviewed gene: TRAPPC6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28626029, 28397838, 31687267; Phenotypes: Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, MIM# 617862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2951 DHX37 Zornitza Stark changed review comment from: Overall, 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype. Green for bi-allelic disease

Much less clear association between mono-allelic variants and ID, two missense variants reported. Note one was mosaic, and for the other, paternal sample was not available, so not confirmed to be de novo. No mechanism for mono-allelic vs bi-allelic disease proposed. Overall, Red for mono-allelic disease causing a neurodevelopmental phenotype at this stage. Note there is a separate association between mono allelic variants and DSD.; to: Overall, 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype. Green for bi-allelic disease

Much less clear association between mono-allelic variants and ID, two missense variants reported. Note one was mosaic, and for the other, paternal sample was not available, so not confirmed to be de novo. No mechanism for mono-allelic vs bi-allelic disease proposed. Overall, Red for mono-allelic variants causing a neurodevelopmental phenotype at this stage. Note there is a separate association between mono allelic variants and DSD.
Intellectual disability syndromic and non-syndromic v0.2951 DHX37 Zornitza Stark changed review comment from: Overall, 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype. Green for bi-allelic disease

Much less clear association between mono-allelic variants and disease, two missense variants reported. Note one was mosaic, and for the other, paternal sample was not available, so not confirmed to be de novo. No mechanism for mono-allelic vs bi-allelic disease proposed. Overall, Red for mono-allelic disease at this stage.; to: Overall, 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype. Green for bi-allelic disease

Much less clear association between mono-allelic variants and ID, two missense variants reported. Note one was mosaic, and for the other, paternal sample was not available, so not confirmed to be de novo. No mechanism for mono-allelic vs bi-allelic disease proposed. Overall, Red for mono-allelic disease causing a neurodevelopmental phenotype at this stage. Note there is a separate association between mono allelic variants and DSD.
Intellectual disability syndromic and non-syndromic v0.2951 DHX37 Zornitza Stark Mode of inheritance for gene: DHX37 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2950 DHX37 Zornitza Stark changed review comment from: Overall, 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype.

Much less clear association between mono-allelic variants and disease, two missense variants reported. Note one was mosaic, and for the other, paternal sample was not available, so not confirmed to be de novo.; to: Overall, 5 unrelated families with bi-allelic variants, all with ID as part of the phenotype. Green for bi-allelic disease

Much less clear association between mono-allelic variants and disease, two missense variants reported. Note one was mosaic, and for the other, paternal sample was not available, so not confirmed to be de novo. No mechanism for mono-allelic vs bi-allelic disease proposed. Overall, Red for mono-allelic disease at this stage.
Intellectual disability syndromic and non-syndromic v0.2950 DHX37 Zornitza Stark Marked gene: DHX37 as ready
Intellectual disability syndromic and non-syndromic v0.2950 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2950 DHX37 Zornitza Stark Classified gene: DHX37 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2950 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2949 DHX37 Zornitza Stark reviewed gene: DHX37: Rating: GREEN; Mode of pathogenicity: None; Publications: 26539891, 31256877; Phenotypes: Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2949 DHX37 Naomi Baker gene: DHX37 was added
gene: DHX37 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DHX37 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DHX37 were set to PMID: 26539891; 31256877
Phenotypes for gene: DHX37 were set to Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, MIM#618731
Review for gene: DHX37 was set to GREEN
Added comment: Two unrelated patients from consanguineous families reported with biallelic missense variants. Clinical presentation included severe microcephaly, DD/ID, and cortical atrophy (PMID: 26539891).

Five individuals who share a phenotype of DD and/or ID and CNS dysfunction. Three out of five individuals also have scoliosis, and two have cardiac phenotypes (PMID: 31256877). Three of the patients had bialleleic missense variants, while two patients had a de novo monoallelic missense variant.

Note that OMIM lists inheritance as biallelic, however two monoallelic cases reportes.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2949 PAK3 Zornitza Stark Marked gene: PAK3 as ready
Intellectual disability syndromic and non-syndromic v0.2949 PAK3 Zornitza Stark Gene: pak3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2949 PAK3 Zornitza Stark Phenotypes for gene: PAK3 were changed from to Mental retardation, X-linked 30/47, MIM# 300558; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.2948 PAK3 Zornitza Stark Publications for gene: PAK3 were set to
Intellectual disability syndromic and non-syndromic v0.2947 PAK3 Zornitza Stark Mode of inheritance for gene: PAK3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2946 PAK3 Zornitza Stark reviewed gene: PAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 9731525, 10946356, 12884430, 17853471, 18523455, 32050918, 32005903, 31943058, 31843706, 31678216; Phenotypes: Mental retardation, X-linked 30/47, MIM# 300558, Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2946 CLTC Zornitza Stark Marked gene: CLTC as ready
Intellectual disability syndromic and non-syndromic v0.2946 CLTC Zornitza Stark Gene: cltc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2946 CLTC Zornitza Stark Phenotypes for gene: CLTC were changed from to Mental retardation, autosomal dominant 56, MIM# 617854
Intellectual disability syndromic and non-syndromic v0.2945 CLTC Zornitza Stark Publications for gene: CLTC were set to
Intellectual disability syndromic and non-syndromic v0.2944 CLTC Zornitza Stark Mode of inheritance for gene: CLTC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2943 CLTC Zornitza Stark reviewed gene: CLTC: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100083, 26822784; Phenotypes: Mental retardation, autosomal dominant 56, MIM# 617854; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2943 PLK4 Zornitza Stark Marked gene: PLK4 as ready
Intellectual disability syndromic and non-syndromic v0.2943 PLK4 Zornitza Stark Gene: plk4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2943 PLK4 Zornitza Stark Phenotypes for gene: PLK4 were changed from to Microcephaly and chorioretinopathy, autosomal recessive, 2, MIM# 616171
Intellectual disability syndromic and non-syndromic v0.2942 PLK4 Zornitza Stark Publications for gene: PLK4 were set to
Intellectual disability syndromic and non-syndromic v0.2941 PLK4 Zornitza Stark Mode of inheritance for gene: PLK4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2940 PLK4 Zornitza Stark reviewed gene: PLK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25344692, 25320347, 27650967; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 2, MIM# 616171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2940 TRAPPC2L Zornitza Stark Marked gene: TRAPPC2L as ready
Intellectual disability syndromic and non-syndromic v0.2940 TRAPPC2L Zornitza Stark Gene: trappc2l has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2940 TRAPPC2L Zornitza Stark Classified gene: TRAPPC2L as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2940 TRAPPC2L Zornitza Stark Gene: trappc2l has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2939 TRAPPC2L Zornitza Stark Tag founder tag was added to gene: TRAPPC2L.
Intellectual disability syndromic and non-syndromic v0.2939 TRAPPC2L Zornitza Stark gene: TRAPPC2L was added
gene: TRAPPC2L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TRAPPC2L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC2L were set to 30120216; 32843486
Phenotypes for gene: TRAPPC2L were set to Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331
Review for gene: TRAPPC2L was set to AMBER
Added comment: Total of three families, but two share a founder variant, and there are some disparities between the clinical presentations reported in the two publications. Rating Amber as additional cases required to delineate the genotype-phenotype relationship. PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect. The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11. PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family. Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2938 DPP6 Zornitza Stark Marked gene: DPP6 as ready
Intellectual disability syndromic and non-syndromic v0.2938 DPP6 Zornitza Stark Gene: dpp6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2938 DPP6 Zornitza Stark Phenotypes for gene: DPP6 were changed from to Mental retardation, autosomal dominant 33 (MIM#616311)
Intellectual disability syndromic and non-syndromic v0.2937 DPP6 Zornitza Stark Publications for gene: DPP6 were set to
Intellectual disability syndromic and non-syndromic v0.2936 DPP6 Zornitza Stark Mode of inheritance for gene: DPP6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2935 DPP6 Zornitza Stark Classified gene: DPP6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2935 DPP6 Zornitza Stark Gene: dpp6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2934 DPP6 Zornitza Stark reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 33 (MIM#616311); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2934 DPP6 Ain Roesley edited their review of gene: DPP6: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2934 DPP6 Ain Roesley reviewed gene: DPP6: Rating: AMBER; Mode of pathogenicity: None; Publications: 23832105; Phenotypes: Mental retardation, autosomal dominant 33 (MIM#616311); Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2934 PCGF2 Zornitza Stark Marked gene: PCGF2 as ready
Intellectual disability syndromic and non-syndromic v0.2934 PCGF2 Zornitza Stark Gene: pcgf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2934 PCGF2 Zornitza Stark Phenotypes for gene: PCGF2 were changed from to Turnpenny-Fry syndrome, MIM# 618371
Intellectual disability syndromic and non-syndromic v0.2933 PCGF2 Zornitza Stark Publications for gene: PCGF2 were set to
Intellectual disability syndromic and non-syndromic v0.2932 PCGF2 Zornitza Stark Mode of inheritance for gene: PCGF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2931 PCGF2 Zornitza Stark reviewed gene: PCGF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30343942; Phenotypes: Turnpenny-Fry syndrome, MIM# 618371; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2931 TRIT1 Zornitza Stark Marked gene: TRIT1 as ready
Intellectual disability syndromic and non-syndromic v0.2931 TRIT1 Zornitza Stark Gene: trit1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2931 TRIT1 Zornitza Stark Phenotypes for gene: TRIT1 were changed from to Combined oxidative phosphorylation deficiency 35, MIM#617873
Intellectual disability syndromic and non-syndromic v0.2930 TRIT1 Zornitza Stark Publications for gene: TRIT1 were set to
Intellectual disability syndromic and non-syndromic v0.2929 TRIT1 Zornitza Stark Mode of inheritance for gene: TRIT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2928 TRIT1 Zornitza Stark reviewed gene: TRIT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32088416, 24901367, 28185376, 30977854; Phenotypes: Combined oxidative phosphorylation deficiency 35, MIM#617873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2928 CREBBP Zornitza Stark Marked gene: CREBBP as ready
Intellectual disability syndromic and non-syndromic v0.2928 CREBBP Zornitza Stark Gene: crebbp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2928 CREBBP Zornitza Stark Phenotypes for gene: CREBBP were changed from to Rubinstein-Taybi syndrome 1, MIM# 180849; Menke-Hennekam syndrome 1, MIM# 618332
Intellectual disability syndromic and non-syndromic v0.2927 CREBBP Zornitza Stark Publications for gene: CREBBP were set to
Intellectual disability syndromic and non-syndromic v0.2926 CREBBP Zornitza Stark Mode of inheritance for gene: CREBBP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2925 CREBBP Zornitza Stark reviewed gene: CREBBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 10699051, 17855048, 27311832, 29460469; Phenotypes: Rubinstein-Taybi syndrome 1, MIM# 180849, Menke-Hennekam syndrome 1, MIM# 618332; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2925 CDC6 Seb Lunke Marked gene: CDC6 as ready
Intellectual disability syndromic and non-syndromic v0.2925 CDC6 Seb Lunke Gene: cdc6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2925 CDC6 Seb Lunke Phenotypes for gene: CDC6 were changed from to Meier-Gorlin syndrome 5 (MIM#613805)
Intellectual disability syndromic and non-syndromic v0.2924 CDC6 Seb Lunke Publications for gene: CDC6 were set to
Intellectual disability syndromic and non-syndromic v0.2923 CDC6 Seb Lunke Mode of inheritance for gene: CDC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2922 CDC6 Seb Lunke Classified gene: CDC6 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2922 CDC6 Seb Lunke Gene: cdc6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2921 CDC6 Ain Roesley reviewed gene: CDC6: Rating: RED; Mode of pathogenicity: None; Publications: 21358632; Phenotypes: Meier-Gorlin syndrome 5 (MIM#613805); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2921 CTNND1 Zornitza Stark Marked gene: CTNND1 as ready
Intellectual disability syndromic and non-syndromic v0.2921 CTNND1 Zornitza Stark Gene: ctnnd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2921 CTNND1 Zornitza Stark Classified gene: CTNND1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2921 CTNND1 Zornitza Stark Gene: ctnnd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2920 CTNND1 Zornitza Stark gene: CTNND1 was added
gene: CTNND1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CTNND1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNND1 were set to 28301459; 32196547
Phenotypes for gene: CTNND1 were set to Blepharocheilodontic syndrome 2, MIM# 617681
Review for gene: CTNND1 was set to AMBER
Added comment: 4 individuals from 3 unrelated families with blepharocheilodontic syndrome and mutations in the CTNND1 gene reported originally in PMID 28301459. All had eyelid anomalies, including ectropion of the lower lids, euryblepharon, lagophthalmia, and distichiasis. In addition, all 4 showed typical facial dysmorphism with hypertelorism, flat face, and high forehead, and all had conical teeth and tooth agenesis. Three had cleft lip and palate, 3 had hair anomalies, and 1 had hypothyroidism due to hypoplasia or aplasia of the thyroid gland. None of the patients exhibited anal atresia or neural tube defects.

PMID: 32196547 - Alharatani et al 2020 - report an expanded phenotype for CTNND1 patients. They report 13 individuals from nine families with novel protein-truncating variants in CTNND1 identified by WES. The mutations were not previously described in blepharocheilodontic (BCD), orofacial cleft cases nor in gnomAD. 8 patients had de novo variants, 2 inherited from affected parents, 2 participants inherited a variant from a parent with a mild phenotype. 8/13 patients showed cleft palate. Additional phenotypic features seen include mild limb phenotypes (9/13), cardiovascular anomalies (6/13) and Developmental delay and other neurodevelopmental problems (8/13).

This more recent publication suggests a broader phenotype associated with CTNND1 variants including dev delay, ADHD/ASD, behavioural issues. Unclear from description whether significant ID present.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2919 ADARB1 Zornitza Stark Phenotypes for gene: ADARB1 were changed from Intellectual disability; microcephaly; seizures to Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862; Intellectual disability; microcephaly; seizures
Intellectual disability syndromic and non-syndromic v0.2918 ADARB1 Zornitza Stark Publications for gene: ADARB1 were set to 32220291
Intellectual disability syndromic and non-syndromic v0.2917 ADARB1 Arina Puzriakova reviewed gene: ADARB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32220291, 32719099; Phenotypes: Neurodevelopmental disorder with hypotonia, microcephaly, and seizures, 618862; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2917 IARS Zornitza Stark Tag new gene name tag was added to gene: IARS.
Intellectual disability syndromic and non-syndromic v0.2917 KIF14 Zornitza Stark Marked gene: KIF14 as ready
Intellectual disability syndromic and non-syndromic v0.2917 KIF14 Zornitza Stark Gene: kif14 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2917 KIF14 Zornitza Stark Phenotypes for gene: KIF14 were changed from to Microcephaly 20, primary, autosomal recessive, MIM# 617914; Meckel syndrome 12, MIM# 616258
Intellectual disability syndromic and non-syndromic v0.2916 KIF14 Zornitza Stark Publications for gene: KIF14 were set to
Intellectual disability syndromic and non-syndromic v0.2915 KIF14 Zornitza Stark Mode of inheritance for gene: KIF14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2914 KIF14 Zornitza Stark reviewed gene: KIF14: Rating: GREEN; Mode of pathogenicity: None; Publications: 28892560, 29343805; Phenotypes: Microcephaly 20, primary, autosomal recessive, MIM# 617914, Meckel syndrome 12, MIM# 616258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2914 MOCS1 Zornitza Stark Marked gene: MOCS1 as ready
Intellectual disability syndromic and non-syndromic v0.2914 MOCS1 Zornitza Stark Gene: mocs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2914 MOCS1 Zornitza Stark Phenotypes for gene: MOCS1 were changed from to Molybdenum cofactor deficiency A, MIM# 252150
Intellectual disability syndromic and non-syndromic v0.2913 MOCS1 Zornitza Stark Publications for gene: MOCS1 were set to
Intellectual disability syndromic and non-syndromic v0.2912 MOCS1 Zornitza Stark Mode of inheritance for gene: MOCS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2911 MOCS1 Zornitza Stark reviewed gene: MOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9921896, 12754701, 21031595; Phenotypes: Molybdenum cofactor deficiency A, MIM# 252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2911 KDM1A Zornitza Stark Marked gene: KDM1A as ready
Intellectual disability syndromic and non-syndromic v0.2911 KDM1A Zornitza Stark Gene: kdm1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2911 KDM1A Zornitza Stark Phenotypes for gene: KDM1A were changed from to Cleft palate, psychomotor retardation, and distinctive facial features 616728
Intellectual disability syndromic and non-syndromic v0.2910 KDM1A Zornitza Stark Publications for gene: KDM1A were set to
Intellectual disability syndromic and non-syndromic v0.2909 KDM1A Zornitza Stark Mode of inheritance for gene: KDM1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2908 KDM1A Zornitza Stark reviewed gene: KDM1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 26656649, 24838796, 27094131; Phenotypes: Cleft palate, psychomotor retardation, and distinctive facial features 616728; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2908 NSD2 Zornitza Stark Marked gene: NSD2 as ready
Intellectual disability syndromic and non-syndromic v0.2908 NSD2 Zornitza Stark Gene: nsd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2908 NSD2 Zornitza Stark Publications for gene: NSD2 were set to
Intellectual disability syndromic and non-syndromic v0.2907 NSD2 Zornitza Stark Phenotypes for gene: NSD2 were changed from to Microcephaly; intellectual disability
Intellectual disability syndromic and non-syndromic v0.2906 NSD2 Zornitza Stark Mode of inheritance for gene: NSD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2905 NSD2 Zornitza Stark reviewed gene: NSD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30345613, 31171569; Phenotypes: Microcephaly, intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2905 AP4E1 Zornitza Stark Marked gene: AP4E1 as ready
Intellectual disability syndromic and non-syndromic v0.2905 AP4E1 Zornitza Stark Gene: ap4e1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2905 AP4E1 Zornitza Stark Phenotypes for gene: AP4E1 were changed from to Spastic paraplegia 51, autosomal recessive, MIM# 613744
Intellectual disability syndromic and non-syndromic v0.2904 AP4E1 Zornitza Stark Publications for gene: AP4E1 were set to
Intellectual disability syndromic and non-syndromic v0.2903 AP4E1 Zornitza Stark Mode of inheritance for gene: AP4E1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2902 AP4E1 Zornitza Stark reviewed gene: AP4E1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20972249, 21620353, 21937992; Phenotypes: Spastic paraplegia 51, autosomal recessive, MIM# 613744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2902 AASS Zornitza Stark Tag disputed tag was added to gene: AASS.
Intellectual disability syndromic and non-syndromic v0.2902 AASS Zornitza Stark Mode of inheritance for gene: AASS was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2901 AASS Zornitza Stark Mode of inheritance for gene: AASS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2900 AASS Zornitza Stark Phenotypes for gene: AASS were changed from to Hyperlysinemia, MIM# 238700
Intellectual disability syndromic and non-syndromic v0.2899 AASS Zornitza Stark Publications for gene: AASS were set to
Intellectual disability syndromic and non-syndromic v0.2898 AASS Zornitza Stark Classified gene: AASS as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2898 AASS Zornitza Stark Gene: aass has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2897 AASS Zornitza Stark reviewed gene: AASS: Rating: AMBER; Mode of pathogenicity: None; Publications: 23570448; Phenotypes: Hyperlysinemia, MIM# 238700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2897 AARS Zornitza Stark Marked gene: AARS as ready
Intellectual disability syndromic and non-syndromic v0.2897 AARS Zornitza Stark Gene: aars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2897 AARS Zornitza Stark Phenotypes for gene: AARS were changed from to Epileptic encephalopathy, early infantile, 29, MIM# 616339
Intellectual disability syndromic and non-syndromic v0.2896 AARS Zornitza Stark Publications for gene: AARS were set to
Intellectual disability syndromic and non-syndromic v0.2896 AARS Zornitza Stark Mode of inheritance for gene: AARS was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2895 AARS Zornitza Stark Mode of inheritance for gene: AARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2894 AARS Zornitza Stark reviewed gene: AARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 28493438, 25817015; Phenotypes: Epileptic encephalopathy, early infantile, 29, MIM# 616339; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2894 PAFAH1B1 Zornitza Stark Marked gene: PAFAH1B1 as ready
Intellectual disability syndromic and non-syndromic v0.2894 PAFAH1B1 Zornitza Stark Gene: pafah1b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2894 PAFAH1B1 Zornitza Stark Phenotypes for gene: PAFAH1B1 were changed from to Lissencephaly 1, MIM# 607432; Subcortical laminar heterotopia, MIM# 607432; MONDO:0011830
Intellectual disability syndromic and non-syndromic v0.2893 PAFAH1B1 Zornitza Stark Publications for gene: PAFAH1B1 were set to
Intellectual disability syndromic and non-syndromic v0.2892 PAFAH1B1 Zornitza Stark Mode of inheritance for gene: PAFAH1B1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2891 PAFAH1B1 Zornitza Stark Tag SV/CNV tag was added to gene: PAFAH1B1.
Intellectual disability syndromic and non-syndromic v0.2891 PAFAH1B1 Zornitza Stark reviewed gene: PAFAH1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11754098, 18285425; Phenotypes: Lissencephaly 1, MIM# 607432, Subcortical laminar heterotopia, MIM# 607432, MONDO:0011830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2891 KIF5C Zornitza Stark Marked gene: KIF5C as ready
Intellectual disability syndromic and non-syndromic v0.2891 KIF5C Zornitza Stark Gene: kif5c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2891 KIF5C Zornitza Stark Phenotypes for gene: KIF5C were changed from to Cortical dysplasia, complex, with other brain malformations 2, MIM# 615282
Intellectual disability syndromic and non-syndromic v0.2890 KIF5C Zornitza Stark Publications for gene: KIF5C were set to
Intellectual disability syndromic and non-syndromic v0.2889 KIF5C Zornitza Stark Mode of inheritance for gene: KIF5C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2888 KIF5C Zornitza Stark reviewed gene: KIF5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 23603762, 23033978, 32562872; Phenotypes: Cortical dysplasia, complex, with other brain malformations 2, MIM# 615282; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2888 DPM3 Zornitza Stark edited their review of gene: DPM3: Changed phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 612937, Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15 618992
Intellectual disability syndromic and non-syndromic v0.2888 GRIN2B Zornitza Stark Marked gene: GRIN2B as ready
Intellectual disability syndromic and non-syndromic v0.2888 GRIN2B Zornitza Stark Gene: grin2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2888 GRIN2B Zornitza Stark Phenotypes for gene: GRIN2B were changed from Mental retardation, autosomal dominant 6, MIM# 613970; Epileptic encephalopathy, early infantile, 27, MIM# 616139 to Mental retardation, autosomal dominant 6, MIM# 613970; Epileptic encephalopathy, early infantile, 27, MIM# 616139
Intellectual disability syndromic and non-syndromic v0.2888 GRIN2B Zornitza Stark Phenotypes for gene: GRIN2B were changed from to Mental retardation, autosomal dominant 6, MIM# 613970; Epileptic encephalopathy, early infantile, 27, MIM# 616139
Intellectual disability syndromic and non-syndromic v0.2887 GRIN2B Zornitza Stark Publications for gene: GRIN2B were set to
Intellectual disability syndromic and non-syndromic v0.2886 GRIN2B Zornitza Stark Mode of inheritance for gene: GRIN2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2885 GRIN2B Zornitza Stark reviewed gene: GRIN2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28377535; Phenotypes: Mental retardation, autosomal dominant 6, MIM# 613970, Epileptic encephalopathy, early infantile, 27, MIM# 616139; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2885 GRIN1 Zornitza Stark Marked gene: GRIN1 as ready
Intellectual disability syndromic and non-syndromic v0.2885 GRIN1 Zornitza Stark Gene: grin1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2885 GRIN1 Zornitza Stark Phenotypes for gene: GRIN1 were changed from to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820
Intellectual disability syndromic and non-syndromic v0.2884 GRIN1 Zornitza Stark Publications for gene: GRIN1 were set to
Intellectual disability syndromic and non-syndromic v0.2883 GRIN1 Zornitza Stark Mode of inheritance for gene: GRIN1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2882 GRIN1 Zornitza Stark reviewed gene: GRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29365063, 27164704, 27164704, 28051072; Phenotypes: Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254, Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2882 HARS Zornitza Stark Publications for gene: HARS were set to 32296180
Intellectual disability syndromic and non-syndromic v0.2881 HARS Zornitza Stark commented on gene: HARS: Please note this is the correct PMID for this disease association
Intellectual disability syndromic and non-syndromic v0.2881 HARS Zornitza Stark reviewed gene: HARS: Rating: AMBER; Mode of pathogenicity: None; Publications: 32333447; Phenotypes: multisystem ataxic syndrome, mild-severe intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2881 ALG12 Zornitza Stark Marked gene: ALG12 as ready
Intellectual disability syndromic and non-syndromic v0.2881 ALG12 Zornitza Stark Gene: alg12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2881 ALG12 Zornitza Stark Phenotypes for gene: ALG12 were changed from to Congenital disorder of glycosylation, type Ig, MIM# 607143
Intellectual disability syndromic and non-syndromic v0.2880 ALG12 Zornitza Stark Publications for gene: ALG12 were set to
Intellectual disability syndromic and non-syndromic v0.2879 ALG12 Zornitza Stark Mode of inheritance for gene: ALG12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2878 ALG12 Zornitza Stark reviewed gene: ALG12: Rating: GREEN; Mode of pathogenicity: None; Publications: 31481313; Phenotypes: Congenital disorder of glycosylation, type Ig, MIM# 607143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2878 ALG11 Zornitza Stark Marked gene: ALG11 as ready
Intellectual disability syndromic and non-syndromic v0.2878 ALG11 Zornitza Stark Gene: alg11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2878 ALG11 Zornitza Stark Phenotypes for gene: ALG11 were changed from to Congenital disorder of glycosylation, type Ip, MIM# 613661
Intellectual disability syndromic and non-syndromic v0.2877 ALG11 Zornitza Stark Publications for gene: ALG11 were set to
Intellectual disability syndromic and non-syndromic v0.2876 ALG11 Zornitza Stark Mode of inheritance for gene: ALG11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2875 ALG11 Zornitza Stark reviewed gene: ALG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 30676690; Phenotypes: Congenital disorder of glycosylation, type Ip, MIM# 613661; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2875 PDE2A Zornitza Stark Marked gene: PDE2A as ready
Intellectual disability syndromic and non-syndromic v0.2875 PDE2A Zornitza Stark Gene: pde2a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2875 PDE2A Zornitza Stark Classified gene: PDE2A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2875 PDE2A Zornitza Stark Gene: pde2a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2874 PDE2A Zornitza Stark gene: PDE2A was added
gene: PDE2A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PDE2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE2A were set to 32467598; 32196122; 29392776
Phenotypes for gene: PDE2A were set to Paroxysmal dyskinesia
Review for gene: PDE2A was set to AMBER
Added comment: Four unrelated families reported with childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, sometimes associated with choreodystonia and interictal baseline EEG abnormalities or epilepsy. One of the reports characterises the disorder as 'Rett-like'. Unclear at this time what proportion of affected individuals have ID as part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2873 CRADD Zornitza Stark Marked gene: CRADD as ready
Intellectual disability syndromic and non-syndromic v0.2873 CRADD Zornitza Stark Gene: cradd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2873 CRADD Zornitza Stark Phenotypes for gene: CRADD were changed from to Mental retardation, autosomal recessive 34, with variant lissencephaly, MIM# 614499
Intellectual disability syndromic and non-syndromic v0.2872 CRADD Zornitza Stark Publications for gene: CRADD were set to
Intellectual disability syndromic and non-syndromic v0.2871 CRADD Zornitza Stark Mode of inheritance for gene: CRADD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2870 CRADD Zornitza Stark reviewed gene: CRADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 27773430; Phenotypes: Mental retardation, autosomal recessive 34, with variant lissencephaly, MIM# 614499; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2870 TDGF1 Zornitza Stark Marked gene: TDGF1 as ready
Intellectual disability syndromic and non-syndromic v0.2870 TDGF1 Zornitza Stark Added comment: Comment when marking as ready: Variant reported is present in 46 hets in gnomad.
Intellectual disability syndromic and non-syndromic v0.2870 TDGF1 Zornitza Stark Gene: tdgf1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2870 TDGF1 Zornitza Stark Tag disputed tag was added to gene: TDGF1.
Intellectual disability syndromic and non-syndromic v0.2870 TMTC3 Zornitza Stark Marked gene: TMTC3 as ready
Intellectual disability syndromic and non-syndromic v0.2870 TMTC3 Zornitza Stark Gene: tmtc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2870 TMTC3 Zornitza Stark Phenotypes for gene: TMTC3 were changed from to Lissencephaly 8 (MIM#617255)
Intellectual disability syndromic and non-syndromic v0.2869 TMTC3 Zornitza Stark Publications for gene: TMTC3 were set to
Intellectual disability syndromic and non-syndromic v0.2868 TMTC3 Zornitza Stark Mode of inheritance for gene: TMTC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2867 TMTC3 Zornitza Stark reviewed gene: TMTC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27773428, 28973161; Phenotypes: Lissencephaly 8 (MIM#617255); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2867 MAOA Zornitza Stark Marked gene: MAOA as ready
Intellectual disability syndromic and non-syndromic v0.2867 MAOA Zornitza Stark Gene: maoa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2867 MAOA Zornitza Stark Phenotypes for gene: MAOA were changed from to Brunner syndrome, MIM# 300615
Intellectual disability syndromic and non-syndromic v0.2866 MAOA Zornitza Stark Publications for gene: MAOA were set to
Intellectual disability syndromic and non-syndromic v0.2865 MAOA Zornitza Stark Mode of inheritance for gene: MAOA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2864 MAOA Zornitza Stark reviewed gene: MAOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25807999, 24169519; Phenotypes: Brunner syndrome, MIM# 300615; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2864 GABRG2 Zornitza Stark Marked gene: GABRG2 as ready
Intellectual disability syndromic and non-syndromic v0.2864 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2864 GABRG2 Zornitza Stark Phenotypes for gene: GABRG2 were changed from to Epileptic encephalopathy, early infantile, 74 618396; Epilepsy, generalized, with febrile seizures plus, type 3 607681
Intellectual disability syndromic and non-syndromic v0.2863 GABRG2 Zornitza Stark Publications for gene: GABRG2 were set to
Intellectual disability syndromic and non-syndromic v0.2862 GABRG2 Zornitza Stark Mode of inheritance for gene: GABRG2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2861 GABRG2 Zornitza Stark reviewed gene: GABRG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11326274, 11326275, 27864268; Phenotypes: Epileptic encephalopathy, early infantile, 74 618396, Epilepsy, generalized, with febrile seizures plus, type 3 607681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2861 GABRB3 Zornitza Stark Marked gene: GABRB3 as ready
Intellectual disability syndromic and non-syndromic v0.2861 GABRB3 Zornitza Stark Gene: gabrb3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2861 GABRB3 Zornitza Stark Phenotypes for gene: GABRB3 were changed from to Epileptic encephalopathy, early infantile, 43, MIM# 617113
Intellectual disability syndromic and non-syndromic v0.2860 GABRB3 Zornitza Stark Publications for gene: GABRB3 were set to
Intellectual disability syndromic and non-syndromic v0.2859 GABRB3 Zornitza Stark Mode of inheritance for gene: GABRB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2858 GABRB3 Zornitza Stark reviewed gene: GABRB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23934111, 27476654; Phenotypes: Epileptic encephalopathy, early infantile, 43, MIM# 617113; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2858 FOLR1 Zornitza Stark Marked gene: FOLR1 as ready
Intellectual disability syndromic and non-syndromic v0.2858 FOLR1 Zornitza Stark Gene: folr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2858 FOLR1 Zornitza Stark Phenotypes for gene: FOLR1 were changed from to Neurodegeneration due to cerebral folate transport deficiency, MIM# 613068
Intellectual disability syndromic and non-syndromic v0.2857 FOLR1 Zornitza Stark Publications for gene: FOLR1 were set to
Intellectual disability syndromic and non-syndromic v0.2856 FOLR1 Zornitza Stark Mode of inheritance for gene: FOLR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2855 FOLR1 Zornitza Stark reviewed gene: FOLR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19732866, 30420205, 27743887; Phenotypes: Neurodegeneration due to cerebral folate transport deficiency, MIM# 613068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2855 LMBRD2 Zornitza Stark reviewed gene: LMBRD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2855 LMBRD2 Zornitza Stark Marked gene: LMBRD2 as ready
Intellectual disability syndromic and non-syndromic v0.2855 LMBRD2 Zornitza Stark Gene: lmbrd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2855 LMBRD2 Zornitza Stark Classified gene: LMBRD2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2855 LMBRD2 Zornitza Stark Gene: lmbrd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2854 KAT5 Zornitza Stark Phenotypes for gene: KAT5 were changed from to Severe global developmental delay; Intellectual disability; Seizures; Microcephaly; Behavioral abnormality; Sleep disturbance; Morphological abnormality of the central nervous system; Short stature; Oral cleft; Abnormality of the face
Intellectual disability syndromic and non-syndromic v0.2853 KAT5 Zornitza Stark Publications for gene: KAT5 were set to
Intellectual disability syndromic and non-syndromic v0.2852 KAT5 Zornitza Stark Mode of pathogenicity for gene: KAT5 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.2851 KAT5 Zornitza Stark Mode of inheritance for gene: KAT5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2850 KAT5 Zornitza Stark Classified gene: KAT5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2850 KAT5 Zornitza Stark Gene: kat5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2849 KAT5 Konstantinos Varvagiannis reviewed gene: KAT5: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 32822602; Phenotypes: Severe global developmental delay, Intellectual disability, Seizures, Microcephaly, Behavioral abnormality, Sleep disturbance, Morphological abnormality of the central nervous system, Short stature, Oral cleft, Abnormality of the face; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2849 LMBRD2 Konstantinos Varvagiannis gene: LMBRD2 was added
gene: LMBRD2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LMBRD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LMBRD2 were set to 32820033; https://doi.org/10.1101/797787
Phenotypes for gene: LMBRD2 were set to Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye
Penetrance for gene: LMBRD2 were set to unknown
Mode of pathogenicity for gene: LMBRD2 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: LMBRD2 was set to AMBER
Added comment: You may consider inclusion with green (13 individuals with dn missense SNVs overall, overlapping features for 10 with available phenotype / a recurring variant has been identified in 2 different studies) or amber rating (role of the gene not known, no variant studies, animal model probably not available).

► Malhotra et al (2020 - PMID: 32820033) report on 10 unrelated individuals with de novo missense LMBRD2 variants.

Features included DD (9/10), ID (6/8 of relevant age), microcephaly (7/10), seizures (5/10 - >=3 different variants), structural brain abnormalities (e.g. thin CC in 6/9), highly variable ocular abnormalities (5/10) and dysmorphic features in some (7/10 - nonspecific).

All had variable prior non-diagnostic genetic tests (CMA, gene panel, mendeliome, karyotype). WES/WGS revealed LMBRD2 missense variants, in all cases de novo. A single individual had additional variants with weaker evidence of pathogenicity.

5 unique missense SNVs and 2 recurrent ones (NM_001007527:c.367T>C - p.Trp123Arg / c.1448G>A - p.Arg483His) were identified. These occurred in different exons. Variants were not present in gnomAD and all had several in silico predictions in favor of a deleterious effect.

There was phenotypic variability among individuals with the same variant (e.g. seizures in 1/3 and microchephaly in 2/3 of those harboring R483H).

The gene has a pLI of 0 (although o/e ranges from 0.23 to 0.55), %HI of 15.13 and z-score of 2.27. The authors presume that haploinsufficiency may not apply, and consider a gain-of-function/dominant-negative effect more likely.

As the authors comment LMBRD2 (LMBR1 domain containing 2) encodes a membrane bound protein with poorly described function. It is widely expressed across tissues with notable expression in human brain (also in Drosophila, or Xenopus laevis). It displays high interspecies conservation.

It has been suggested (Paek et al - PMID: 28388415) that LMBRD2 is a potential regulator of β2 adrenoreceptor signalling through involvement in GPCR signalling.

► Kaplanis et al (2020 - https://doi.org/10.1101/797787) in a dataset of 31058 parent-offspring trios (WES) previously identified 3 individuals with developmental disorder, harboring c.1448G>A - p.Arg483His. These individuals (1 from the DDD study, and 2 GeneDx patients) appear in Decipher. [ https://decipher.sanger.ac.uk/ddd/research-variant/40e17c78cc9655a6721006fc1e0c98db/overview ]. The preprint by Kaplanis et al is cited by Malhotra et al, with Arg483His reported in 6 patients overall in both studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2849 TMEM237 Zornitza Stark Marked gene: TMEM237 as ready
Intellectual disability syndromic and non-syndromic v0.2849 TMEM237 Zornitza Stark Gene: tmem237 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2849 TMEM237 Zornitza Stark Phenotypes for gene: TMEM237 were changed from to Joubert syndrome 14, MIM# 614424
Intellectual disability syndromic and non-syndromic v0.2848 TMEM237 Zornitza Stark Publications for gene: TMEM237 were set to
Intellectual disability syndromic and non-syndromic v0.2847 TMEM237 Zornitza Stark Mode of inheritance for gene: TMEM237 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2846 TMEM237 Zornitza Stark reviewed gene: TMEM237: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152675; Phenotypes: Joubert syndrome 14, MIM# 614424; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2846 KANSL1 Zornitza Stark Marked gene: KANSL1 as ready
Intellectual disability syndromic and non-syndromic v0.2846 KANSL1 Zornitza Stark Gene: kansl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2846 KANSL1 Zornitza Stark Phenotypes for gene: KANSL1 were changed from to Koolen-De Vries syndrome (MIM#610443)
Intellectual disability syndromic and non-syndromic v0.2845 KANSL1 Zornitza Stark Publications for gene: KANSL1 were set to
Intellectual disability syndromic and non-syndromic v0.2844 KANSL1 Zornitza Stark Mode of inheritance for gene: KANSL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2843 KANSL1 Zornitza Stark reviewed gene: KANSL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22544363; Phenotypes: Koolen-De Vries syndrome (MIM#610443); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2843 TAOK1 Zornitza Stark Marked gene: TAOK1 as ready
Intellectual disability syndromic and non-syndromic v0.2843 TAOK1 Zornitza Stark Gene: taok1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2843 TAOK1 Zornitza Stark Phenotypes for gene: TAOK1 were changed from to Intellectual disability; hypotonia; macrocephaly
Intellectual disability syndromic and non-syndromic v0.2842 TAOK1 Zornitza Stark Publications for gene: TAOK1 were set to
Intellectual disability syndromic and non-syndromic v0.2841 TAOK1 Zornitza Stark Mode of inheritance for gene: TAOK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2840 TAOK1 Sue White commented on gene: TAOK1: Monoallelic de novo variants reported in 8 individuals with nonspecific phenotype of intellectual disability and hypotonia. Most were LOF, 2 missense. 3 had macrocephaly.
Intellectual disability syndromic and non-syndromic v0.2840 TAOK1 Sue White reviewed gene: TAOK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31230721; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2840 RAI1 Zornitza Stark Marked gene: RAI1 as ready
Intellectual disability syndromic and non-syndromic v0.2840 RAI1 Zornitza Stark Gene: rai1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2840 RAI1 Zornitza Stark Phenotypes for gene: RAI1 were changed from to Smith-Magenis syndrome (MIM#182290)
Intellectual disability syndromic and non-syndromic v0.2839 RAI1 Zornitza Stark Publications for gene: RAI1 were set to
Intellectual disability syndromic and non-syndromic v0.2838 RAI1 Zornitza Stark Mode of inheritance for gene: RAI1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2837 RAI1 Zornitza Stark reviewed gene: RAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11404004, 12652298, 15788730; Phenotypes: Smith-Magenis syndrome (MIM#182290); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2837 TAF1C Zornitza Stark Classified gene: TAF1C as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2837 TAF1C Zornitza Stark Gene: taf1c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2836 TAF1C Konstantinos Varvagiannis gene: TAF1C was added
gene: TAF1C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TAF1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF1C were set to 32779182
Phenotypes for gene: TAF1C were set to Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology
Penetrance for gene: TAF1C were set to Complete
Review for gene: TAF1C was set to AMBER
Added comment: Knuutinen et al (2020 - PMID: 32779182) report on 2 individuals from 2 consanguineous families, homozygous for TAF1C missense variants.

Both presented with an early onset neurological phenotype with severe global DD, ID (2/2 - moderate and profound), spasticity (2/2), ophthalmic findings (strabismus 2/2, nystagmus 1/2). Epilepsy, abnormal brain MRI (cerebral and cerebellar atrophy and white matter hyperintensities) as well and additional findings were reported in one (always the same individual).

Following a normal CMA, exome in the first case revealed a homozygous missense SNV (NM_005679.3:c.1165C>T / p.Arg389Cys) supported by in silico predictions. mRNA and protein levels were substantially reduced in fibroblasts from this subject. Only the patient and parents were tested for the variant but not 3 unaffected sibs (fig1).

The second individual was homozygous for another missense variant (p.Arg405Cys) also supported by in silico predictions. The girl was the single affected person within the family with an unaffected sib and parents heterozygous for the variant. Several other unaffected relatives in the extended pedigree were either carriers for this variant or homozygous for the wt allele.

TAF1C encodes the TATA-box binding protein associated factor (TAF) RNA polymerase I subunit.

RNA polymerase I (Pol I) transcribes genes to produce rRNA. For Pol I to initiate transcription, two transcription factors are required : UBF (upstream binding factor encoded by UBTF) and SL1 (selectivity factor 1). The latter is formed by TBP (TATA-binding protein) and 3 Pol I-specific TBP-associated factors (TAFs).

A recurrent de novo missense variant in UBTF (encoding the other Pol I transcription factor) causes a disorder with highly similar features. The specific variant acts through a gain-of-function mechanism (and not by LoF which appears to apply for TAF1C based on expression data).

The authors hypothesize that altered Pol I activity and resulting ribosomal stress could cause the microcephaly and leukodystrophy (both reported in 1 - the same - individual).

As a result, TAF1C may be considered for inclusion in the ID panel with amber rating pending further evidence.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2836 KAT8 Zornitza Stark Phenotypes for gene: KAT8 were changed from Intellectual disability; seizures; autism; dysmorphic features to Intellectual disability; seizures; autism; dysmorphic features; Li-Ghorbani-Weisz syndrome, MIM#618974
Intellectual disability syndromic and non-syndromic v0.2835 MADD Konstantinos Varvagiannis reviewed gene: MADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 29302074, 32761064; Phenotypes: Global developmental delay / Intellectual disability / Seizures, Global developmental delay / Intellectual disability / Seizures / Abnormality of the endocrine system / Exocrine pancreatic insufficiency / Constipation / Diarrhea / Anemia / Thrombocytopenia / Abnormality of the autonomic nervous system; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2835 SLC5A6 Zornitza Stark Phenotypes for gene: SLC5A6 were changed from Developmental delay; epilepsy; neurodegeneration to Developmental delay; epilepsy; neurodegeneration; Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Intellectual disability syndromic and non-syndromic v0.2834 FAM50A Zornitza Stark Marked gene: FAM50A as ready
Intellectual disability syndromic and non-syndromic v0.2834 FAM50A Zornitza Stark Gene: fam50a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2834 FAM50A Zornitza Stark Classified gene: FAM50A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2834 FAM50A Zornitza Stark Gene: fam50a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2833 FAM50A Konstantinos Varvagiannis gene: FAM50A was added
gene: FAM50A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FAM50A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: FAM50A were set to 32703943
Phenotypes for gene: FAM50A were set to Mental retardation syndrome, X-linked, Armfield type (MIM #300261)
Penetrance for gene: FAM50A were set to unknown
Review for gene: FAM50A was set to GREEN
Added comment: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference.

The authors provide clinical details on 6 affected individuals from 5 families.

Features included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6).

In the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam).

In affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40).

Missense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3).

Previous studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones).

Immunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt.

Complementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish.

Similarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins.

Overall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism.

Several other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.).

Please consider inclusion in the ID panel with green rating and epilepsy panel with amber (seizures in individuals from 2 families).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2833 ADK Zornitza Stark Marked gene: ADK as ready
Intellectual disability syndromic and non-syndromic v0.2833 ADK Zornitza Stark Gene: adk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2833 ADK Zornitza Stark Phenotypes for gene: ADK were changed from to Hypermethioninemia due to adenosine kinase deficiency, MIM# 614300
Intellectual disability syndromic and non-syndromic v0.2832 ADK Zornitza Stark Publications for gene: ADK were set to
Intellectual disability syndromic and non-syndromic v0.2831 ADK Zornitza Stark Mode of inheritance for gene: ADK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2830 ADK Zornitza Stark reviewed gene: ADK: Rating: GREEN; Mode of pathogenicity: None; Publications: 21963049, 17120046; Phenotypes: Hypermethioninemia due to adenosine kinase deficiency, MIM# 614300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2830 SOX6 Zornitza Stark Phenotypes for gene: SOX6 were changed from ADHD; Craniosynostosis; Osteochondromas to ADHD; Craniosynostosis; Osteochondromas; Tolchin-Le Caignec syndrome, MIM#618971
Intellectual disability syndromic and non-syndromic v0.2829 SOX6 Zornitza Stark edited their review of gene: SOX6: Changed rating: GREEN; Changed phenotypes: Tolchin-Le Caignec syndrome, MIM#618971; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2829 HYLS1 Zornitza Stark Tag founder tag was added to gene: HYLS1.
Intellectual disability syndromic and non-syndromic v0.2829 HYLS1 Zornitza Stark Classified gene: HYLS1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2829 HYLS1 Zornitza Stark Gene: hyls1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2828 HYLS1 Zornitza Stark changed review comment from: Given that generally most affected individuals die in utero or shortly after birth, this is probably not the right panel for this gene.; to: Single family reported with Joubert phenotype, generally most affected individuals with hydrolethalus die in utero or shortly after birth so would not present with ID. Note founder variant in Finnish population associated with the hydrolethalus phenotype.
Intellectual disability syndromic and non-syndromic v0.2828 HYLS1 Zornitza Stark edited their review of gene: HYLS1: Changed rating: AMBER; Changed publications: 15843405, 18648327, 19400947, 19656802, 32509774, 26830932
Intellectual disability syndromic and non-syndromic v0.2828 RAC1 Zornitza Stark Marked gene: RAC1 as ready
Intellectual disability syndromic and non-syndromic v0.2828 RAC1 Zornitza Stark Gene: rac1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2828 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from Mental retardation, autosomal dominant 48, MIM# 617751 to Mental retardation, autosomal dominant 48, MIM# 617751
Intellectual disability syndromic and non-syndromic v0.2827 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from Mental retardation, autosomal dominant 48 617751 to Mental retardation, autosomal dominant 48, MIM# 617751
Intellectual disability syndromic and non-syndromic v0.2827 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from to Mental retardation, autosomal dominant 48 617751
Intellectual disability syndromic and non-syndromic v0.2826 RAC1 Zornitza Stark Publications for gene: RAC1 were set to
Intellectual disability syndromic and non-syndromic v0.2825 RAC1 Zornitza Stark Mode of pathogenicity for gene: RAC1 was changed from to Other
Intellectual disability syndromic and non-syndromic v0.2824 RAC1 Zornitza Stark Mode of inheritance for gene: RAC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2823 RAC1 Zornitza Stark edited their review of gene: RAC1: Changed phenotypes: Mental retardation, autosomal dominant 48 617751
Intellectual disability syndromic and non-syndromic v0.2823 RAC1 Zornitza Stark reviewed gene: RAC1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30042656, 29276006, 30293988; Phenotypes: Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (MIM#618577), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2823 BCOR Zornitza Stark Marked gene: BCOR as ready
Intellectual disability syndromic and non-syndromic v0.2823 BCOR Zornitza Stark Gene: bcor has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2823 BCOR Zornitza Stark Phenotypes for gene: BCOR were changed from to Microphthalmia, syndromic 2, MIM# 300166; Oculofaciocardiodental syndrome; Lenz microphthalmia
Intellectual disability syndromic and non-syndromic v0.2822 BCOR Zornitza Stark Publications for gene: BCOR were set to
Intellectual disability syndromic and non-syndromic v0.2821 BCOR Zornitza Stark Mode of inheritance for gene: BCOR was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2820 BCOR Zornitza Stark reviewed gene: BCOR: Rating: GREEN; Mode of pathogenicity: None; Publications: 29974297; Phenotypes: Microphthalmia, syndromic 2, MIM# 300166, Oculofaciocardiodental syndrome, Lenz microphthalmia; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2820 ARSE Zornitza Stark Marked gene: ARSE as ready
Intellectual disability syndromic and non-syndromic v0.2820 ARSE Zornitza Stark Added comment: Comment when marking as ready: Note HGNC approved name is ARSL.
Intellectual disability syndromic and non-syndromic v0.2820 ARSE Zornitza Stark Gene: arse has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2820 ARSE Zornitza Stark Phenotypes for gene: ARSE were changed from to Chondrodysplasia punctata, X-linked recessive, MIM# 302950
Intellectual disability syndromic and non-syndromic v0.2819 ARSE Zornitza Stark Publications for gene: ARSE were set to
Intellectual disability syndromic and non-syndromic v0.2818 ARSE Zornitza Stark Mode of inheritance for gene: ARSE was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2817 ARSE Zornitza Stark Tag new gene name tag was added to gene: ARSE.
Intellectual disability syndromic and non-syndromic v0.2817 ARSE Zornitza Stark reviewed gene: ARSE: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301713; Phenotypes: Chondrodysplasia punctata, X-linked recessive, MIM# 302950; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2817 FBXO11 Zornitza Stark Marked gene: FBXO11 as ready
Intellectual disability syndromic and non-syndromic v0.2817 FBXO11 Zornitza Stark Gene: fbxo11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2817 FBXO11 Zornitza Stark Phenotypes for gene: FBXO11 were changed from to Intellectual Developmental Disorder with Dysmorphic Facies and Behavioural Abnormalities, MIM#618089
Intellectual disability syndromic and non-syndromic v0.2816 FBXO11 Zornitza Stark Mode of inheritance for gene: FBXO11 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2815 FBXO11 Zornitza Stark Publications for gene: FBXO11 were set to
Intellectual disability syndromic and non-syndromic v0.2815 FBXO11 Zornitza Stark Mode of inheritance for gene: FBXO11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2814 FBXO11 Vivian WEI reviewed gene: FBXO11: Rating: GREEN; Mode of pathogenicity: None; Publications: 30679813, 30057029, 29796876; Phenotypes: Intellectual Developmental Disorder with Dysmorphic Facies and Behavioural Abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.2814 PIGQ Zornitza Stark Marked gene: PIGQ as ready
Intellectual disability syndromic and non-syndromic v0.2814 PIGQ Zornitza Stark Gene: pigq has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2814 PIGQ Zornitza Stark Classified gene: PIGQ as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2814 PIGQ Zornitza Stark Gene: pigq has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2813 PIGQ Konstantinos Varvagiannis gene: PIGQ was added
gene: PIGQ was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PIGQ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGQ were set to 32588908; 24463883; 25558065; 31148362
Phenotypes for gene: PIGQ were set to Epileptic encephalopathy, early infantile, 77 (MIM #618548)
Penetrance for gene: PIGQ were set to Complete
Review for gene: PIGQ was set to GREEN
Added comment: Homozygous or compound heterozygous mutations in PIGQ cause Epileptic encephalopathy, early infantile, 77 (MIM #618548).

Johnstone et al (2020 - PMID: 32588908) describe the phenotype of 7 children (from 6 families) with biallelic PIGQ pathogenic variants. The authors also review the phenotype of 3 subjects previously reported in the literature (by Martin et al, Alazami et al, Starr et al - respective PMIDs: 24463883, 25558065, 31148362).

Affected individuals displayed severe to profound global DD/ID and seizures with onset in the first year of life. There were variable other features incl. - among others - genitourinary, cardiac, skeletal, ophthalmological anomalies, gastrointestinal issues. Within the cohort there was significant morbidity/mortality.

PIGQ encodes phosphatidylinositol glycan anchor biosynthesis class Q protein, playing a role (early) in the biosynthesis of the GPI-anchor. Several genes in the GPI biosynthesis pathway cause multi-system disease with DD/ID and seizures. Flow cytometry has been used in individuals with PIGQ-related disorder. Serum ALP was elevated in some (4) although - as the authors comment - elevations are more typical in disorders affecting later steps of GPI biosynthesis.

More than 10 variants have been reported to date (missense / pLoF).

Overall PIGQ can be considered for green rating in both ID and epilepsy gene panels.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2813 HPDL Zornitza Stark Marked gene: HPDL as ready
Intellectual disability syndromic and non-syndromic v0.2813 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2813 HPDL Zornitza Stark Phenotypes for gene: HPDL were changed from Progressive neurological disorder to Progressive neurological disorder; Leigh-like syndrome
Intellectual disability syndromic and non-syndromic v0.2812 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2812 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2811 HPDL Crystle Lee gene: HPDL was added
gene: HPDL was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086
Phenotypes for gene: HPDL were set to Progressive neurological disorder
Review for gene: HPDL was set to GREEN
Added comment: Biallelic variants reported in 13 families with a neurodegenerative disease ranging from neonatal encephalopathy to adolescent-onset spastic paraplegia
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2811 PIGP Seb Lunke Publications for gene: PIGP were set to 28334793; 31139695
Intellectual disability syndromic and non-syndromic v0.2810 PIGP Seb Lunke Classified gene: PIGP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2810 PIGP Seb Lunke Gene: pigp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2809 PIGP Seb Lunke reviewed gene: PIGP: Rating: GREEN; Mode of pathogenicity: None; Publications: 32042915; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2809 SCAF4 Zornitza Stark Marked gene: SCAF4 as ready
Intellectual disability syndromic and non-syndromic v0.2809 SCAF4 Zornitza Stark Gene: scaf4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2809 SCAF4 Zornitza Stark Classified gene: SCAF4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2809 SCAF4 Zornitza Stark Gene: scaf4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2808 PJA1 Zornitza Stark Tag founder tag was added to gene: PJA1.
Intellectual disability syndromic and non-syndromic v0.2808 PJA1 Zornitza Stark Marked gene: PJA1 as ready
Intellectual disability syndromic and non-syndromic v0.2808 PJA1 Zornitza Stark Gene: pja1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2808 PJA1 Zornitza Stark Classified gene: PJA1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2808 PJA1 Zornitza Stark Gene: pja1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2807 PJA1 Zornitza Stark gene: PJA1 was added
gene: PJA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PJA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PJA1 were set to 32530565
Phenotypes for gene: PJA1 were set to Intellectual disability; trigonocephaly
Review for gene: PJA1 was set to AMBER
Added comment: Recurrent variant, p.Arg376Cys, reported in 7 Japanese individuals, supportive mouse model. Individuals shared a common haplotype, suggestive of founder effect.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2806 SCAF4 Crystle Lee gene: SCAF4 was added
gene: SCAF4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: SCAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCAF4 were set to 32730804
Phenotypes for gene: SCAF4 were set to Mild intellectual disability; seizures; behavioral abnormalities
Review for gene: SCAF4 was set to GREEN
Added comment: > 5 variants reported in individuals with variable neurodevelopmental disorder characterized by mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2806 NARS Zornitza Stark Marked gene: NARS as ready
Intellectual disability syndromic and non-syndromic v0.2806 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2806 NARS Zornitza Stark Classified gene: NARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2806 NARS Zornitza Stark Gene: nars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2805 NARS Zornitza Stark Tag new gene name tag was added to gene: NARS.
Intellectual disability syndromic and non-syndromic v0.2805 NARS Konstantinos Varvagiannis changed review comment from: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]

Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families.

Similar features were reported for AR/AD occurrences of the disorder and included of microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features.

NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.

Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].

The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).

As also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy.
Sources: Literature; to: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]

Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families.

Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features.

NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.

Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].

The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).

As also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2805 NARS Konstantinos Varvagiannis gene: NARS was added
gene: NARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225
Phenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy
Penetrance for gene: NARS were set to Complete
Review for gene: NARS was set to GREEN
Added comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1]

Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families.

Similar features were reported for AR/AD occurrences of the disorder and included of microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features.

NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported.

Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all].

The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model).

As also Manole et al suggest, NARS1 can be considered for inclusion in gene panels for DD/ID, epilepsy and/or demyelinating neuropathy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2805 ZNF407 Zornitza Stark Marked gene: ZNF407 as ready
Intellectual disability syndromic and non-syndromic v0.2805 ZNF407 Zornitza Stark Added comment: Comment when marking as ready: Evidence both for mono allelic and bi-allelic disease, though neither sufficient for Green rating at present.
Intellectual disability syndromic and non-syndromic v0.2805 ZNF407 Zornitza Stark Gene: znf407 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2805 ZNF407 Zornitza Stark Classified gene: ZNF407 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2805 ZNF407 Zornitza Stark Gene: znf407 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2804 ZNF407 Konstantinos Varvagiannis gene: ZNF407 was added
gene: ZNF407 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZNF407 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ZNF407 were set to 24907849; 32737394; 23195952
Phenotypes for gene: ZNF407 were set to Global developmental delay; Intellectual disability
Penetrance for gene: ZNF407 were set to unknown
Review for gene: ZNF407 was set to AMBER
Added comment: You may consider inclusion of this gene probably with amber rating (or green if the evidence for biallelic variants is considered sufficient).

Biallelic variants:

- Kambouris et al. (2014 - PMID: 24907849) described 2 brothers with severe DD and ID, born to first cousin parents. Homozygosity mapping, following other non-diagnostic investigations (incl. aCGH), revealed 4 major homozygosity intervals. Exome sequencing in one identified 5 variants within these intervals, ZNF407 (c.5054C>G, p.Ser1685Trp) being the best candidate, supported also by segregation studies. The authors commented that zinc finger proteins act as transcriptional regulators, with mutations in genes encoding for other zinc finger proteins interfering with normal brain development.

- Zahra et al. (2020 - PMID: 32737394) report on 7 affected individuals (from 3 families) homozygous or compound heterozygous for ZNF407 variants. Features included hypotonia, DD and ID (in all) and variable occurrence of short stature (6/6), microcephaly (in at least 5), behavioural, visual problems and deafness. Linkage analysis in the first family revealed a 4.4 Mb shared homozygosity region and exome (30x) revealed a 3-bp duplication, confirmed by Sanger sequencing and segregating with the disease (NM_001146189:c.2814_2816dup, p.Val939dup). Affected subjects from the 2 other families were each found to be homozygous (c.2405G>T) or compound heterozygous (c.2884C>G, c.3642G>C) for other variants. Segregation was compatible in all families. Other studies were not performed. The authors comment than only the 3-bp duplication fullfilled ACMG criteria for classification as LP, the other variants being all formally classified as VUS (also due to in silico predictions predicting a LB effect). In addition, while several features such as DD/ID and short stature appeared to be frequent among all patients reported, Zahra et all comment that there was partial clinical overlap with the sibs described by Kambouris et al (additional variants?).


Monoallelic disruption of ZNF407:

- Ren et al (2013 - PMID: 23195952) described an 8 y.o. boy with ID and ASD. The boy was found to harbor a de novo translocation between chromosomes 3 and 18 [46,XY,t(3;18)(p13;q22.3)]. Array CGH did not reveal any P/LP CNV. Delineation of the breakpoints (FISH, long-range PCR) revealed that the chr18 breakpoint disrupted intron 3 of ZNF407 (isoform 1) with the other breakpoint within a gene-free region of exon 3. There was a loss of 4-8 nt in chr18 and 2-6 in chr3. Sequencing of ZNF407 did not reveal additional variants. RNA isolation in blood followed by RT-PCR studied expression of all 3 ZNF407 isoforms (the intronic region being shared by isoforms 1 and 2). Expression of isoform 1 was shown to be significantly reduced compared to controls. Isoform 2 was undetectable (in blood) while isoform 3 expression was similar to controls. Sequencing of 105 additional patients with similar clinical presentation (ID & ASD) revealed 2 further individuals with de novo missense variants.

- Based on the discussion by Kambouris et al (PMID: 24907849 - cited literature not here reviewed) ZNF407 may be deleted in patients with congenital aural atresia due to deletion of a critical region of 18q22.3 (though TSHZ1 is responsible for this phenotype) or 18q- although such deletions span several other genes (cited PMID: 16639285). In one case the breakpoint was shown to be disrupting ZNF407 (cited PMID: 24092497).

- The denovo db and Decipher (research variant tab) list few individuals with de novo ZNF407 SNVs although these do not seem to allow conclusions.

https://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=ZNF407
https://decipher.sanger.ac.uk/search/ddd-research-variants/results?q=znf407
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2804 MAPK1 Zornitza Stark Marked gene: MAPK1 as ready
Intellectual disability syndromic and non-syndromic v0.2804 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2804 MAPK1 Zornitza Stark Classified gene: MAPK1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2804 MAPK1 Zornitza Stark Gene: mapk1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2803 MAPK1 Konstantinos Varvagiannis gene: MAPK1 was added
gene: MAPK1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAPK1 were set to 32721402
Phenotypes for gene: MAPK1 were set to Global developmental delay; Intellectual disability; Behavioral abnormality; Growth delay; Abnormality of the face; Abnormality of the neck; Abnormality of the cardiovascular system; Abnormality of the skin
Penetrance for gene: MAPK1 were set to unknown
Mode of pathogenicity for gene: MAPK1 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: MAPK1 was set to GREEN
Added comment: Motta et al (2020 - PMID: 32721402) report on 7 unrelated individuals harboring de novo missense MAPK1 pathogenic variants.

The phenotype corresponded to a neurodevelopmental disorder and - as the authors comment - consistently included DD, ID , behavioral problems. Postnatal growth delay was observed in approximately half. Hypertelorism, ptosis, downslant of palpebral fissures, wide nasal bridge as low-set/posteriorly rotated ears were among the facial features observed (each in 3 or more subjects within this cohort). Together with short/webbed neck and abnormalities of skin (lentigines / CAL spots) and growth delay these led to clinical suspicion of Noonan s. or disorder of the same pathway in some. Congenital heart defects (ASD, mitral valve insufficiency, though not cardiomyopathy) occurred in 4/7. Bleeding diathesis and lymphedema were reported only once.

MAPK1 encodes the mitogen-activated protein kinase 1 (also known as ERK2) a serine/threonine kinase of the RAS-RAF-MEK-(MAPK/)ERK pathway.

MAPK1 de novo variants were identified in all individuals following trio exome sequencing (and extensive previous genetic investigations which were non-diagnostic).

The distribution of variants, as well as in silico/vitro/vivo studies suggest a GoF effect (boosted signal through the MAPK cascade. MAPK signaling also upregulated in Noonan syndrome).

The authors comment that screening of 267 additional individuals with suspected RASopathy (without mutations in previously implicated genes) did not reveal other MAPK1 variants.

Overall this gene can be considered for inclusion in the ID panel with green rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2803 ASPM Zornitza Stark Marked gene: ASPM as ready
Intellectual disability syndromic and non-syndromic v0.2803 ASPM Zornitza Stark Gene: aspm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2803 ASPM Zornitza Stark Phenotypes for gene: ASPM were changed from to Microcephaly 5, primary, autosomal recessive, MIM#608716
Intellectual disability syndromic and non-syndromic v0.2802 ASPM Zornitza Stark Publications for gene: ASPM were set to
Intellectual disability syndromic and non-syndromic v0.2801 ASPM Zornitza Stark Mode of inheritance for gene: ASPM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2800 ASPM Zornitza Stark reviewed gene: ASPM: Rating: GREEN; Mode of pathogenicity: None; Publications: 29243349, 19028728; Phenotypes: Microcephaly 5, primary, autosomal recessive, MIM#608716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2800 TUBB2A Zornitza Stark Marked gene: TUBB2A as ready
Intellectual disability syndromic and non-syndromic v0.2800 TUBB2A Zornitza Stark Gene: tubb2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2800 TUBB2A Zornitza Stark Phenotypes for gene: TUBB2A were changed from to Cortical dysplasia, complex, with other brain malformations 5, MIM# 615763
Intellectual disability syndromic and non-syndromic v0.2799 TUBB2A Zornitza Stark Publications for gene: TUBB2A were set to
Intellectual disability syndromic and non-syndromic v0.2798 TUBB2A Zornitza Stark Mode of inheritance for gene: TUBB2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2797 TUBB2A Zornitza Stark reviewed gene: TUBB2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32571897; Phenotypes: Cortical dysplasia, complex, with other brain malformations 5, MIM# 615763; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2797 EEF1A2 Zornitza Stark Marked gene: EEF1A2 as ready
Intellectual disability syndromic and non-syndromic v0.2797 EEF1A2 Zornitza Stark Gene: eef1a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2797 EEF1A2 Zornitza Stark Phenotypes for gene: EEF1A2 were changed from to Epileptic encephalopathy, early infantile, 33, MIM# 616409; Mental retardation, autosomal dominant 38, MIM# 616393
Intellectual disability syndromic and non-syndromic v0.2796 EEF1A2 Zornitza Stark Publications for gene: EEF1A2 were set to
Intellectual disability syndromic and non-syndromic v0.2795 EEF1A2 Zornitza Stark Mode of pathogenicity for gene: EEF1A2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.2794 EEF1A2 Zornitza Stark Mode of inheritance for gene: EEF1A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2793 EEF1A2 Zornitza Stark reviewed gene: EEF1A2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 32160274; Phenotypes: Epileptic encephalopathy, early infantile, 33, MIM# 616409, Mental retardation, autosomal dominant 38, MIM# 616393; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2793 TASP1 Zornitza Stark Phenotypes for gene: TASP1 were changed from Developmental delay; microcephaly; dysmorphic features; congenital abnormalities to Developmental delay; microcephaly; dysmorphic features; congenital abnormalities; Suleiman-El-Hattab syndrome, MIM#618950
Intellectual disability syndromic and non-syndromic v0.2792 TASP1 Zornitza Stark edited their review of gene: TASP1: Changed phenotypes: Developmental delay, microcephaly, dysmorphic features, congenital abnormalities, Suleiman-El-Hattab syndrome, MIM#618950
Intellectual disability syndromic and non-syndromic v0.2792 LARS Zornitza Stark Tag new gene name tag was added to gene: LARS.
Intellectual disability syndromic and non-syndromic v0.2792 LARS Zornitza Stark Marked gene: LARS as ready
Intellectual disability syndromic and non-syndromic v0.2792 LARS Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name LARS1
Intellectual disability syndromic and non-syndromic v0.2792 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2792 LARS Zornitza Stark Phenotypes for gene: LARS were changed from Infantile liver failure syndrome 1, MIM# 615438 to Infantile liver failure syndrome 1, MIM# 615438; Seizures; Intellectual disability; Encephalopathy
Intellectual disability syndromic and non-syndromic v0.2791 LARS Zornitza Stark Classified gene: LARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2791 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2790 LARS Konstantinos Varvagiannis gene: LARS was added
gene: LARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS were set to 32699352
Phenotypes for gene: LARS were set to Infantile liver failure syndrome 1, MIM# 615438
Penetrance for gene: LARS were set to Complete
Review for gene: LARS was set to GREEN
Added comment: Please consider inclusion with amber/green rating in the current panel.

Biallelic pathogenic LARS1 variants cause Infantile liver failure syndrome 1, MIM# 615438.

Lenz et al (2020 - PMID: 32699352) review the phenotype of 25 affected individuals from 15 families.

Seizures occurred in 19/24 and were commonly associated with infections. Encephalopathic episodes (in 13 patients) accompanied by seizures up to status epilepticus occurred independently of hepatic decompensation.

In addition 22/24 presented with neurodevelopmental delay. The authors comment that cognitive impairment was present in 13/17 individuals (mild-severe) whereas most presented with learning disabilities.

These patients will most likely investigated for their liver disease (although presentation was highly variable and/or very mild in few).

The gene encodes a cytoplasmic amino-acyl tRNA synthetase (ARS) with neurologic manifestations observed in almost all patients (and seizures / DD and ID common to other disorders due to mutations in other genes encoding for ARSs).

Please note that the HGNC approved symbol for this gene is LARS1.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2790 SMARCA2 Zornitza Stark Marked gene: SMARCA2 as ready
Intellectual disability syndromic and non-syndromic v0.2790 SMARCA2 Zornitza Stark Gene: smarca2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2790 SMARCA2 Zornitza Stark Phenotypes for gene: SMARCA2 were changed from to Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome
Intellectual disability syndromic and non-syndromic v0.2789 SMARCA2 Zornitza Stark Publications for gene: SMARCA2 were set to
Intellectual disability syndromic and non-syndromic v0.2788 SMARCA2 Zornitza Stark Mode of pathogenicity for gene: SMARCA2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.2787 SMARCA2 Zornitza Stark Mode of inheritance for gene: SMARCA2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2786 MORC2 Zornitza Stark reviewed gene: MORC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32693025; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2786 MORC2 Zornitza Stark Marked gene: MORC2 as ready
Intellectual disability syndromic and non-syndromic v0.2786 MORC2 Zornitza Stark Gene: morc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2786 MORC2 Zornitza Stark Phenotypes for gene: MORC2 were changed from Charcot-Marie-Tooth disease, axonal, type 2Z, MIM #616688 to Charcot-Marie-Tooth disease, axonal, type 2Z, MIM #616688; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.2785 MORC2 Zornitza Stark Publications for gene: MORC2 were set to https://doi.org/10.1016/j.ajhg.2020.06.013
Intellectual disability syndromic and non-syndromic v0.2784 MORC2 Zornitza Stark Classified gene: MORC2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2784 MORC2 Zornitza Stark Gene: morc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2783 SMARCA2 Konstantinos Varvagiannis reviewed gene: SMARCA2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 26468571, 32694869; Phenotypes: Nicolaides-Baraitser syndrome, MIM #601358, Blepharophimosis-intellectual disability syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.2783 MORC2 Konstantinos Varvagiannis gene: MORC2 was added
gene: MORC2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MORC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MORC2 were set to https://doi.org/10.1016/j.ajhg.2020.06.013
Phenotypes for gene: MORC2 were set to Charcot-Marie-Tooth disease, axonal, type 2Z, MIM #616688
Penetrance for gene: MORC2 were set to unknown
Mode of pathogenicity for gene: MORC2 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: MORC2 was set to GREEN
Added comment: The current review is based on a recent report by Sacoto et al (2020 - https://doi.org/10.1016/j.ajhg.2020.06.013).

While several previous studies focused on the phenotype of axonal motor and senory neuropathy in individuals with heterozygous MORC2 pathogenic variants (Charcot-Marie-Tooth disease, axonal, type 2Z, MIM #616688) some of them presented among others with hypotonia, muscle weakness, intellectual disability, microcephaly or hearing loss [refs provided by Sacoto et al - learning disabilities (in some patients) also listed in OMIM's clinical synopsis].

Sacoto et al present a cohort of 20 individuals having genetic testing for developmental delay or growth failure (with a single one for a diagnosis of sensorimotor neuropathy).

Overlapping features included DD, ID (18/20 - mild to severe), short stature (18/20), microcephaly (15/20) and variable craniofacial dysmorphisms. The authors comment that features suggestive of neuropathy (weakness, hyporeflexia, abnormal EMG/NCS) were frequent but not the predominant complaint. EMG/NCS abnormalities were abnormal in 6 out of 10 subjects investigated in this cohort. Other findings included brain MRI abnormalities (12/18 - in 5/18 Leigh-like lesions), hearing loss (11/19) and pigmentary retinopathy in few (5).

Affected subjects were found to harbor in all cases missense variants in the ATPase module of MORC2 [residues 1 to 494 - NM_001303256.1 - the module consists of an ATPase domain (aa 1-265), a transducer S5-like domain (266-494) and a coiled-coiled domain (CC1 - aa 282-361)].

Variants had occured mostly as de novo events although inheritance from a similarly affected parent was also reported.

Some of them were recurring within this cohort and/or the literature eg. c.79G>A/p.Glu27Lys (x5), c.260C>T/p.Ser87Leu (x2), c.394C>T/p.Arg132Cys (4x), c.1164C>G/p.Ser388Arg (x2), c.1181A>G/p.Tyr394Cys (x3).

MORC2 encodes an ATPase involved in chromatin remodeling, DNA repair and transcriptional regulation. Chromatin remodeling and epigenetic silencing by MORC2 is mediated by the HUSH (Human Silencing Hub) complex. Functional studies (MORC2-knockout HeLa cells harboring a HUSH-sensitive GFP reporter were transduced with wt or mt MORC2 followed by measurement of reporter repression) supported the deleterious effect of most variants known at the time (hyperactivation of HUSH-mediating silencing, in line with previous observations).

Overall this gene can be considered for inclusion in the ID panel with green rating. Also other gene panels (e.g. for short stature, microcephaly, hearing loss, pigmentary retinopathy, etc) if it meets the respective criteria for inclusion.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2783 HDAC8 Zornitza Stark Marked gene: HDAC8 as ready
Intellectual disability syndromic and non-syndromic v0.2783 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2783 HDAC8 Zornitza Stark Phenotypes for gene: HDAC8 were changed from to Cornelia de Lange syndrome 5, MIM# 300882
Intellectual disability syndromic and non-syndromic v0.2782 HDAC8 Zornitza Stark Publications for gene: HDAC8 were set to
Intellectual disability syndromic and non-syndromic v0.2781 HDAC8 Zornitza Stark Mode of inheritance for gene: HDAC8 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2780 HDAC8 Zornitza Stark reviewed gene: HDAC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 30614194, 24403048; Phenotypes: Cornelia de Lange syndrome 5, MIM# 300882; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2779 NSDHL Zornitza Stark Marked gene: NSDHL as ready
Intellectual disability syndromic and non-syndromic v0.2779 NSDHL Zornitza Stark Gene: nsdhl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2779 NSDHL Zornitza Stark Phenotypes for gene: NSDHL were changed from to CK syndrome (MIM#300831)
Intellectual disability syndromic and non-syndromic v0.2778 NSDHL Zornitza Stark Publications for gene: NSDHL were set to
Intellectual disability syndromic and non-syndromic v0.2777 NSDHL Zornitza Stark Mode of inheritance for gene: NSDHL was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2776 NSDHL Crystle Lee reviewed gene: NSDHL: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129721, 15689440, 25900314; Phenotypes: CK syndrome (MIM#300831); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2776 ZNF462 Zornitza Stark Phenotypes for gene: ZNF462 were changed from Weiss-Kruszka syndrome; OMIM# 618619 to Weiss-Kruszka syndrome, OMIM# 618619
Intellectual disability syndromic and non-syndromic v0.2775 ZNF462 Zornitza Stark Publications for gene: ZNF462 were set to PubMed: 31361404; 28513610
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Marked gene: DEAF1 as ready
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Gene: deaf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Phenotypes for gene: DEAF1 were changed from to Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171; Vulto-van Silfout-de Vries syndrome 615828
Intellectual disability syndromic and non-syndromic v0.2773 DEAF1 Zornitza Stark Publications for gene: DEAF1 were set to
Intellectual disability syndromic and non-syndromic v0.2772 DEAF1 Zornitza Stark Mode of inheritance for gene: DEAF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2771 DEAF1 Zornitza Stark reviewed gene: DEAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30923367, 24726472, 26048982, 28940898, 26834045; Phenotypes: Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171, Vulto-van Silfout-de Vries syndrome 615828; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2771 GRM7 Zornitza Stark Phenotypes for gene: GRM7 were changed from Epilepsy, microcephaly, developmental delay to Epilepsy, microcephaly, developmental delay; neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Intellectual disability syndromic and non-syndromic v0.2770 GRM7 Zornitza Stark edited their review of gene: GRM7: Changed phenotypes: Epilepsy, microcephaly, developmental delay, neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA), MIM#618922
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Marked gene: LHX3 as ready
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Gene: lhx3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2770 LHX3 Zornitza Stark Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3 (MIM#221750)
Intellectual disability syndromic and non-syndromic v0.2769 LHX3 Zornitza Stark Publications for gene: LHX3 were set to
Intellectual disability syndromic and non-syndromic v0.2768 LHX3 Zornitza Stark Mode of inheritance for gene: LHX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2767 LHX3 Zornitza Stark Classified gene: LHX3 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2767 LHX3 Zornitza Stark Gene: lhx3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2766 LHX3 Crystle Lee reviewed gene: LHX3: Rating: RED; Mode of pathogenicity: None; Publications: 28302169; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM#221750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2766 ATL1 Zornitza Stark Marked gene: ATL1 as ready
Intellectual disability syndromic and non-syndromic v0.2766 ATL1 Zornitza Stark Gene: atl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2766 ATL1 Zornitza Stark Phenotypes for gene: ATL1 were changed from to Neuropathy, hereditary sensory, type ID, MIM# 613708; Spastic paraplegia 3A, autosomal dominant, MIM# 182600
Intellectual disability syndromic and non-syndromic v0.2765 ATL1 Zornitza Stark Publications for gene: ATL1 were set to
Intellectual disability syndromic and non-syndromic v0.2764 ATL1 Zornitza Stark Mode of inheritance for gene: ATL1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2763 ATL1 Zornitza Stark Classified gene: ATL1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2763 ATL1 Zornitza Stark Gene: atl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2762 ATL1 Zornitza Stark reviewed gene: ATL1: Rating: RED; Mode of pathogenicity: None; Publications: 21336785, 28736820, 29180453, 29691679, 31236401; Phenotypes: Neuropathy, hereditary sensory, type ID, MIM# 613708, Spastic paraplegia 3A, autosomal dominant, MIM# 182600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Marked gene: CNPY3 as ready
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Classified gene: CNPY3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2762 CNPY3 Zornitza Stark Gene: cnpy3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Classified gene: KIF21B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2761 KIF21B Zornitza Stark Gene: kif21b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Marked gene: PAX1 as ready
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Classified gene: PAX1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Classified gene: PAX1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Gene: pax1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Marked gene: TMEM106B as ready
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Classified gene: TMEM106B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Marked gene: TBC1D2B as ready
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Classified gene: TBC1D2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Marked gene: EXOC2 as ready
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Classified gene: EXOC2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Marked gene: CEP120 as ready
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Classified gene: CEP120 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Marked gene: CCDC174 as ready
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Classified gene: CCDC174 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Gene: ccdc174 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Marked gene: ACOX2 as ready
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Gene: acox2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Classified gene: ACOX2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Gene: acox2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Marked gene: ABCA2 as ready
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Classified gene: ABCA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Gene: abca2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2752 HERC2 Zornitza Stark Publications for gene: HERC2 were set to 23243086; 23065719
Intellectual disability syndromic and non-syndromic v0.2751 HERC2 Zornitza Stark Classified gene: HERC2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2751 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2750 TTI1 Zornitza Stark commented on gene: TTI1: Two unrelated consanguineous families previously described with homozygous missense variants, both in large cohort papers with multiple candidate genes in inbred population. No functional evidence provided, segregation uninformative.
Intellectual disability syndromic and non-syndromic v0.2750 CNPY3 Konstantinos Varvagiannis gene: CNPY3 was added
gene: CNPY3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CNPY3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNPY3 were set to 29394991; 30237576
Phenotypes for gene: CNPY3 were set to Epileptic encephalopathy, early infantile, 60 (MIM 617929)
Penetrance for gene: CNPY3 were set to Complete
Review for gene: CNPY3 was set to GREEN
Added comment: Biallelic CNPY3 mutations cause Epileptic encephalopathy, early infantile, 60 (MIM 617929).

The phenotype including among others hypotonia, intractable seizures, DD and ID has been first reported by Mutoh et al (2018 - PMID: 29394991) in 3 subjects from 2 families. Evidence was provided for the role of the gene (incl. mouse model) and pathogenicity of the identified variants (resulting in LoF).

Another subject with similar features of hypotonia, DD, intractable epilepsy, feeding problems has been described briefly by Maddirevula et al (2019 - PMID: 30237576).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 KIF21B Konstantinos Varvagiannis gene: KIF21B was added
gene: KIF21B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KIF21B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KIF21B were set to 32415109
Phenotypes for gene: KIF21B were set to Global developmental delay; Intellectual disability; Abnormality of brain morphology; Microcephaly
Penetrance for gene: KIF21B were set to unknown
Mode of pathogenicity for gene: KIF21B 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: KIF21B was set to GREEN
Added comment: Asselin et al (2020 - PMID: 32415109) report on 4 individuals with KIF21B pathogenic variants. DD/ID (borderline intellectual functioning to severe ID) was a feature in all. Variable other findings included brain malformations (CCA) and microcephaly. 3 missense variants and a 4-bp insertion were identified, in 3 cases as de novo events while in a single subject the variant was inherited from the father who was also affected. The authors provide evidence for a role of KIF21B in the regulation of processes involved in cortical development and deleterious effect of the missense variants impeding neuronal migration and kinesin autoinhibition. Phenotypes specific to variants (e.g. CCA or microcephaly) were recapitulated in animal models. Missense variants are thought to exert a gain-of-function effect. As commented on, the 4-bp duplication (/frameshift) variant might not be pathogenic. In blood sample from the respective individual, RT-qPCR analysis suggested that haploinsufficiency (NMD) applies. Although Kif21b haploinsufficiency in mice was shown to lead to impaired neuronal positioning, the gene might partially tolerate LoF variants as also suggested by 28 such variants in gnomAD. Homozygous Kif21b ko mice display severe morphological abnormalities, partial loss of commissural fibers, cognitive deficits and altered synaptic transmission (several refs to previous studies provided by the authors).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 PAX1 Konstantinos Varvagiannis gene: PAX1 was added
gene: PAX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature,Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: PAX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAX1 were set to 29681087; 23851939; 28657137
Phenotypes for gene: PAX1 were set to Otofaciocervical syndrome 2, 615560
Penetrance for gene: PAX1 were set to Complete
Review for gene: PAX1 was set to AMBER
Added comment: Biallelic PAX1 pathogenic variants cause Otofaciocervical syndrome 2 (OMIM 615560).

Brief review of the literature suggests 3 relevant publications to date (04-07-2020).

2 individuals with DD and ID have been reported (Patil et al, 2018 - PMID: 29681087 and Pohl et al, 2013 - PMID: 23851939). Other subjects reported were only evaluated as newborns(mostly)/infants [Paganini et al, 2017 - PMID: 28657137, Patil et al, 2018 - PMID: 29681087].

While the first report by Pohl et al identified a homozygous missense variant supported by functional studies [NM_006192.5:c.497G>T - p.(Gly166Val)] subsequent ones identified homozygosity for pLoF mutations [Patil et al: NM_006192.4:c.1173_1174insGCCCG / Paganini et al: NM_006192:c.1104C>A - p.(Cys368*)].

As discussed by Pohl et al:

PAX1 encodes a transcription factor with critical role in pattern formation during embryogenesis. Study of the mouse Gly157Val (equivalent to human Gly166Val) Pax1 variant suggested reduced binding affinity (reduced transactivation of a regulatory sequence of the Nkx3-2 promoter) and hypofunctional nature of this variant.

Mouse models seem to recapitulate features of the disorder (skeletal, immunodeficiency) while the role of Pax1 in hearing process was thought to be supported by early expression (P6) in mouse cochlea.

Overall this gene can be considered for inclusion in the ID panel with amber/green rating.
Sources: Literature, Radboud University Medical Center, Nijmegen
Intellectual disability syndromic and non-syndromic v0.2750 TMEM106B Konstantinos Varvagiannis gene: TMEM106B was added
gene: TMEM106B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TMEM106B were set to 29186371; 29444210; 32595021
Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964)
Penetrance for gene: TMEM106B were set to Complete
Mode of pathogenicity for gene: TMEM106B 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: TMEM106B was set to GREEN
Added comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 - PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021).

While a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al].

All harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al).

As discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin.

Recurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect.

Genes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel.

Overall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 TBC1D2B Konstantinos Varvagiannis gene: TBC1D2B was added
gene: TBC1D2B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Penetrance for gene: TBC1D2B were set to Complete
Review for gene: TBC1D2B was set to AMBER
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants.

Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations.

All were born to non-consanguineous couples and additional investigations were performed in some.

Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses.

In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts.

TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation.

Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.

Overall this gene can be considered for inclusion with amber/green rating in the ID panel and green in epilepsy panel.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 EXOC2 Konstantinos Varvagiannis gene: EXOC2 was added
gene: EXOC2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Penetrance for gene: EXOC2 were set to Complete
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations.

Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3).

Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals.

EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis.

Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration.

An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2.

Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome).

The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 CEP120 Konstantinos Varvagiannis gene: CEP120 was added
gene: CEP120 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP120 were set to 27208211
Phenotypes for gene: CEP120 were set to Joubert syndrome 31 (MIM 617761); Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300)
Penetrance for gene: CEP120 were set to Complete
Review for gene: CEP120 was set to GREEN
Added comment: Pathogenic CEP120 variants have been reported in recessive ciliopathies, namely Short-rib thoracic dysplasia 13 with or without polydactyly (MIM 616300) and Joubert syndrome 31 (MIM 617761).

The former is associated with a severe/lethal outcome (4 unrelated infants described by Shaheen et al 2015 - PMID: 25361962, 2 fetuses reported by Roosing et al 2016 - PMID: 27208211).

Roosing et al however, also provided details on 4 unrelated subjects with Joubert syndrome diagnosis. All presented with a neurologic phenotype of hypotonia, DD, cognitive impairment and exhibited a molar tooth sign.

As a result, this gene can be considered for inclusion in the ID panel with green rating (>3 individuals/variants, consistent ciliopathy phenotype).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 CCDC174 Konstantinos Varvagiannis gene: CCDC174 was added
gene: CCDC174 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCDC174 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC174 were set to 26358778
Phenotypes for gene: CCDC174 were set to Hypotonia, infantile, with psychomotor retardation - IHPMR, 616816
Penetrance for gene: CCDC174 were set to Complete
Mode of pathogenicity for gene: CCDC174 was set to Other
Review for gene: CCDC174 was set to AMBER
Added comment: Biallelic pathogenic CCDC174 variants cause Hypotonia, infantile, with psychomotor retardation - IHPMR (MIM 616816).

Volodarsky et al [2015 - PMID: 26358778] describe 6 children from 2 unrelated families with - among others - severe hypotonia, psychomotor delay and abducens nerve palsy. All affected subjects were homozygous for a stoploss variant. Evidence from functional studies/animal model is provided supporting the role of the gene in this phenotype.

Overall this gene can be considered for inclusion in the ID panel with amber rating (2 families, single founder variant, consistent phenotype, supportive studies) pending further reports.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 ACOX2 Konstantinos Varvagiannis gene: ACOX2 was added
gene: ACOX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACOX2 were set to 27647924; 27884763; 29287774
Phenotypes for gene: ACOX2 were set to Bile acid synthesis defect, congenital, 6 - 617308
Penetrance for gene: ACOX2 were set to unknown
Review for gene: ACOX2 was set to RED
Added comment: Biallelic pathogenic ACOX2 variants cause Bile acid synthesis defect, congenital, 6 (MIM 617308). Overall the phenotype corresponds to an IEM/peroxisomal disorder.

As per 01-07-2020 there are 3 reports, briefly reviewed :

- Vilarinho et al [2016 - PMID: 27647924] provided details on an 8-year-old boy with ID.
- Monte et al [2017 - PMID: 27884763] described a 16 year old male with sustained elevation of transaminases *without* accompanying neurologic symptomatology (as they comment).
- Ferdinandusse et al [2018 - PMID: 29287774] reported on a girl deceased at the age of few months.

Please consider inclusion in the ID panel with amber/red rating pending further reports.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 ABCA2 Konstantinos Varvagiannis gene: ABCA2 was added
gene: ABCA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799
Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808
Penetrance for gene: ABCA2 were set to Complete
Review for gene: ABCA2 was set to GREEN
Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808).

There are 3 relevant publications (01-07-2020) :
- Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations.
- Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures.
- Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype.

All subjects harbored biallelic pLoF variants.

N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency.

Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2750 HERC2 Konstantinos Varvagiannis reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2750 RPL10 Zornitza Stark Phenotypes for gene: RPL10 were changed from to Mental retardation, X-linked, syndromic, 35 (MIM#300998)
Intellectual disability syndromic and non-syndromic v0.2749 RPL10 Zornitza Stark Publications for gene: RPL10 were set to
Intellectual disability syndromic and non-syndromic v0.2748 RPL10 Zornitza Stark Mode of inheritance for gene: RPL10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2747 RPL10 Crystle Lee reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: 25316788, 26290468, 25846674, 29066376; Phenotypes: Mental retardation, X-linked, syndromic, 35 (MIM#300998); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2747 GLS Zornitza Stark Mode of pathogenicity for gene: GLS was changed from None to Other
Intellectual disability syndromic and non-syndromic v0.2746 GLS Zornitza Stark Publications for gene: GLS were set to 30970188
Intellectual disability syndromic and non-syndromic v0.2745 GLS Zornitza Stark Classified gene: GLS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2745 GLS Zornitza Stark Gene: gls has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2744 GLS Zornitza Stark edited their review of gene: GLS: Added comment: Another three individuals from two unrelated families reported with early neonatal refractory seizures, structural brain abnormalities and oedema; significantly increased glutamine levels (PMID: 30575854).; Changed rating: GREEN; Changed publications: 30970188, 30239721, 30575854; Changed phenotypes: Epileptic encephalopathy, early infantile, 71, MIM# 618328, Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Marked gene: PLCB1 as ready
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2744 PLCB1 Zornitza Stark Phenotypes for gene: PLCB1 were changed from to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
Intellectual disability syndromic and non-syndromic v0.2743 PLCB1 Zornitza Stark Publications for gene: PLCB1 were set to
Intellectual disability syndromic and non-syndromic v0.2742 PLCB1 Zornitza Stark Tag SV/CNV tag was added to gene: PLCB1.
Intellectual disability syndromic and non-syndromic v0.2742 PLCB1 Zornitza Stark Mode of inheritance for gene: PLCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Marked gene: PIGY as ready
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2741 PIGY Zornitza Stark Phenotypes for gene: PIGY were changed from to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
Intellectual disability syndromic and non-syndromic v0.2740 PIGY Zornitza Stark Publications for gene: PIGY were set to
Intellectual disability syndromic and non-syndromic v0.2739 PIGY Zornitza Stark Mode of inheritance for gene: PIGY was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2738 PIGY Zornitza Stark Classified gene: PIGY as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2738 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2737 PLCB1 Crystle Lee reviewed gene: PLCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24684524, 20833646, 22690784, 26818157; Phenotypes: Epileptic encephalopathy, early infantile, 12 (MIM#613722); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2737 HIST1H4C Seb Lunke Classified gene: HIST1H4C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2737 HIST1H4C Seb Lunke Gene: hist1h4c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2736 HIST1H4C Seb Lunke reviewed gene: HIST1H4C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2736 CNOT1 Chern Lim reviewed gene: CNOT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32553196; Phenotypes: Neurodevelopmental delay; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.2736 SLC12A2 Seb Lunke Phenotypes for gene: SLC12A2 were changed from Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation to Kilquist syndrome; deafness; intellectual disability; dysmorphic features; absent salivation; ectodermal dysplasia; constipation; intestinal malrotation; multiple congenital anomalies
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Classified gene: SLC12A2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Added comment: Comment on list classification: Two independent families and mouse model
Intellectual disability syndromic and non-syndromic v0.2735 SLC12A2 Seb Lunke Gene: slc12a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2734 SLC12A2 Seb Lunke reviewed gene: SLC12A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Marked gene: RAP1GDS1 as ready
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Classified gene: RAP1GDS1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2734 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2733 RAP1GDS1 Zornitza Stark gene: RAP1GDS1 was added
gene: RAP1GDS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAP1GDS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAP1GDS1 were set to 32431071
Phenotypes for gene: RAP1GDS1 were set to Intellectual disability; dysmorphic features
Review for gene: RAP1GDS1 was set to AMBER
Added comment: Four individuals from two consanguineous families, same homozygous splice site variant detected.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2732 SETD1B Zornitza Stark Publications for gene: SETD1B were set to 32546566
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark changed review comment from: At least 4 unrelated individuals reported.; to: At least 7 unrelated individuals reported.
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark edited their review of gene: SETD1B: Changed publications: 32546566, 29322246, 31440728, 31685013
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Marked gene: SETD1B as ready
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Gene: setd1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2731 SETD1B Zornitza Stark Phenotypes for gene: SETD1B were changed from to SETD1B-related neurodevelopmental disorder
Intellectual disability syndromic and non-syndromic v0.2730 SETD1B Zornitza Stark Publications for gene: SETD1B were set to
Intellectual disability syndromic and non-syndromic v0.2729 SETD1B Zornitza Stark Mode of inheritance for gene: SETD1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2728 SETD1B Zornitza Stark reviewed gene: SETD1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32546566; Phenotypes: SETD1B-related neurodevelopmental disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2728 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from Intellectual disability; seizures; PVNH; dysmorphic features to Intellectual disability; seizures; PVNH; dysmorphic features; Periventricular nodular heterotopia 9, MIM# 618918
Intellectual disability syndromic and non-syndromic v0.2727 MAP1B Zornitza Stark edited their review of gene: MAP1B: Changed phenotypes: Intellectual disability, seizures, PVNH, dysmorphic features, Periventricular nodular heterotopia 9, MIM# 618918
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Marked gene: CAPZA2 as ready
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Classified gene: CAPZA2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2727 CAPZA2 Zornitza Stark Gene: capza2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2726 CAPZA2 Zornitza Stark gene: CAPZA2 was added
gene: CAPZA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CAPZA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAPZA2 were set to 32338762
Phenotypes for gene: CAPZA2 were set to Intellectual disability
Review for gene: CAPZA2 was set to AMBER
Added comment: PMID: 32338762 - Huang et al 2020 - report 2 unrelated families (Chinese and European) in which a de novo heterozygous variant has been identified in CAPZA2 in paediatric probands that present with global motor development delay, speech delay, intellectual disability, hypotonia. One proband had seizures at 7 months but these were controlled with medication and did not repeat. The other proband at age one had an atypical febrile seizure that was controlled without medication. Functional studies in Drosophila suggest that these variants are mild loss of function mutations but that they can act as dominant negative variants in actin polymerization in bristles.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2725 EXOC7 Zornitza Stark Marked gene: EXOC7 as ready
Intellectual disability syndromic and non-syndromic v0.2725 EXOC7 Zornitza Stark Gene: exoc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2725 HNRNPH1 Zornitza Stark Marked gene: HNRNPH1 as ready
Intellectual disability syndromic and non-syndromic v0.2725 HNRNPH1 Zornitza Stark Gene: hnrnph1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Classified gene: PDCD6IP as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Gene: pdcd6ip has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2724 MCM3AP Zornitza Stark edited their review of gene: MCM3AP: Added comment: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; Changed publications: 32202298
Intellectual disability syndromic and non-syndromic v0.2724 MCM3AP Zornitza Stark Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Intellectual disability syndromic and non-syndromic v0.2723 MCM3AP Zornitza Stark edited their review of gene: MCM3AP: Changed publications: 24123876, 28633435, 28969388, 29982295, 32202298
Intellectual disability syndromic and non-syndromic v0.2723 EXOC7 Chirag Patel Classified gene: EXOC7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2723 EXOC7 Chirag Patel Gene: exoc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2722 EXOC7 Chirag Patel gene: EXOC7 was added
gene: EXOC7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EXOC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC7 were set to PMID: 32103185
Phenotypes for gene: EXOC7 were set to brain atrophy; seizures; developmental delay; microcephaly
Review for gene: EXOC7 was set to GREEN
Added comment: 4 families with 8 affected individuals with brain atrophy, seizures, and developmental delay, and in more severe cases microcephaly and infantile death. Four novel homozygous or comp.heterozygous variants found in EXOC7, which segregated with disease in the families. They showed that EXOC7, a member of the mammalian exocyst complex, is highly expressed in developing human cortex. In addition, a zebrafish model of Exoc7 deficiency recapitulates the human disorder with increased apoptosis and decreased progenitor cells during telencephalon development, suggesting that the brain atrophy in human cases reflects neuronal degeneration.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2721 HNRNPH1 Chirag Patel Classified gene: HNRNPH1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2721 HNRNPH1 Chirag Patel Gene: hnrnph1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2720 HNRNPH1 Chirag Patel gene: HNRNPH1 was added
gene: HNRNPH1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HNRNPH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPH1 were set to PMID: 32335897; 29938792
Phenotypes for gene: HNRNPH1 were set to HNRNPH1 ‐related syndromic intellectual disability
Review for gene: HNRNPH1 was set to GREEN
Added comment: 1st patient reported in 2018 with intellectual disability and dysmorphic features and HNRNPH1 heterozygous missense variant.

2020 paper reports additional 7 cases with ID, short stature, microcephaly, distinctive dysmorphic facial features, and congenital anomalies (cranial, brain, genitourinary, palate, ophthalmologic). They all had HNRNPH1 heterozygous pathogenic variants (missense, frameshift, in‐frame deletion, entire gene duplication) and were identified using clinical networks and GeneMatcher. No comments in paper if all de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2719 PDCD6IP Chirag Patel gene: PDCD6IP was added
gene: PDCD6IP was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PDCD6IP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD6IP were set to PMID: 32286682
Phenotypes for gene: PDCD6IP were set to Primary microcephaly
Review for gene: PDCD6IP was set to RED
Added comment: One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2718 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Intellectual disability syndromic and non-syndromic v0.2717 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929
Intellectual disability syndromic and non-syndromic v0.2717 GRIA2 Zornitza Stark Phenotypes for gene: GRIA2 were changed from no OMIM number yet to Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917
Intellectual disability syndromic and non-syndromic v0.2716 GRIA2 Zornitza Stark reviewed gene: GRIA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31300657; Phenotypes: Neurodevelopmental disorder with language impairment and behavioral abnormalities, MIM# 618917; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2716 CDK19 Zornitza Stark Phenotypes for gene: CDK19 were changed from Intellectual disability; epileptic encephalopathy to Intellectual disability; epileptic encephalopathy; Epileptic encephalopathy, early infantile, 87, MIM# 618916
Intellectual disability syndromic and non-syndromic v0.2715 CDK19 Zornitza Stark edited their review of gene: CDK19: Changed phenotypes: Intellectual disability, epileptic encephalopathy, Epileptic encephalopathy, early infantile, 87, MIM# 618916
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2715 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from to Luscan-Lumish syndrome, MIM#616831
Intellectual disability syndromic and non-syndromic v0.2714 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Intellectual disability syndromic and non-syndromic v0.2713 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2712 SETD2 Zornitza Stark reviewed gene: SETD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681085; Phenotypes: Luscan-Lumish syndrome, MIM#616831; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Marked gene: UBE2A as ready
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Gene: ube2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2712 UBE2A Zornitza Stark Phenotypes for gene: UBE2A were changed from to Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860)
Intellectual disability syndromic and non-syndromic v0.2711 UBE2A Zornitza Stark Publications for gene: UBE2A were set to
Intellectual disability syndromic and non-syndromic v0.2710 UBE2A Zornitza Stark Mode of inheritance for gene: UBE2A was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2709 UBE2A Crystle Lee reviewed gene: UBE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24053514, 16909393; Phenotypes: Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Marked gene: HARS as ready
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Classified gene: HARS as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2709 HARS Bryony Thompson Gene: hars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2708 HARS Bryony Thompson gene: HARS was added
gene: HARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS were set to 32296180
Phenotypes for gene: HARS were set to multisystem ataxic syndrome; mild-severe intellectual disability
Review for gene: HARS was set to AMBER
Added comment: 3 cases from 2 unrelated families with biallelic variants and mild to severe intellectual disability as a feature of the condition.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark reviewed gene: GOLGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Marked gene: GOLGA2 as ready
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Classified gene: GOLGA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2707 GOLGA2 Zornitza Stark Gene: golga2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Marked gene: SIL1 as ready
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Gene: sil1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2706 SIL1 Zornitza Stark Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome (MIM#248800)
Intellectual disability syndromic and non-syndromic v0.2705 SIL1 Zornitza Stark Publications for gene: SIL1 were set to
Intellectual disability syndromic and non-syndromic v0.2704 SIL1 Zornitza Stark Mode of inheritance for gene: SIL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2703 GOLGA2 Elena Savva gene: GOLGA2 was added
gene: GOLGA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GOLGA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOLGA2 were set to PMID: 30237576; 26742501
Phenotypes for gene: GOLGA2 were set to Neuromuscular disorder
Review for gene: GOLGA2 was set to AMBER
Added comment: PMID: 30237576 - One 11 year old patient with a homozygous PTC.
Patient had global dev delay, microcephaly, distal muscle weakness with joint contractures and elevated CK levels. Muscle biopsy showed dystrophin changes. MRI at 2 years old showed brain atrophy with thin corpus callosum and hypomyelination. No seizures or regression.

PMID: 26742501 - One infant with a homozygous PTC.
Patient had dev delay, seizures, microcephaly and muscular dystrophy. Zebrafish null model recapitulates the human phenotype with microcephaly and skeletal muscle disorganization.

Summary: 2 patients
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2703 SIL1 Crystle Lee reviewed gene: SIL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24176978, 16282977; Phenotypes: Marinesco-Sjogren syndrome (MIM#248800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2703 TANC2 Zornitza Stark Phenotypes for gene: TANC2 were changed from no OMIM number yet; Intellectual disability; autism; epilepsy; dysmorphism to Intellectual disability; autism; epilepsy; dysmorphism; Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Intellectual disability syndromic and non-syndromic v0.2702 TANC2 Zornitza Stark reviewed gene: TANC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Gene: nexmif has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2702 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from to Mental retardation, X-linked 98, MIM# 300912
Intellectual disability syndromic and non-syndromic v0.2701 NEXMIF Zornitza Stark Publications for gene: NEXMIF were set to
Intellectual disability syndromic and non-syndromic v0.2700 NEXMIF Zornitza Stark Mode of inheritance for gene: NEXMIF was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2699 NEXMIF Zornitza Stark reviewed gene: NEXMIF: Rating: GREEN; Mode of pathogenicity: None; Publications: 27358180; Phenotypes: Mental retardation, X-linked 98 300912; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2699 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Intellectual disability syndromic and non-syndromic v0.2699 FBXW11 Zornitza Stark Phenotypes for gene: FBXW11 were changed from Intellectual disability; developmental eye anomalies; digital anomalies to Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Intellectual disability; developmental eye anomalies; digital anomalies
Intellectual disability syndromic and non-syndromic v0.2698 FBXW11 Zornitza Stark reviewed gene: FBXW11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental, eye, jaw, and digital syndrome (NDEJD), MIM#618914; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Marked gene: SCN3A as ready
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2698 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Intellectual disability syndromic and non-syndromic v0.2697 SCN3A Zornitza Stark Publications for gene: SCN3A were set to
Intellectual disability syndromic and non-syndromic v0.2696 SCN3A Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other
Intellectual disability syndromic and non-syndromic v0.2695 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2694 SCN3A Zornitza Stark reviewed gene: SCN3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 32515017; Phenotypes: Epilepsy, familial focal, with variable foci 4, MIM# 617935, Epileptic encephalopathy, early infantile, 62, MIM# 617938, Intellectual disability, Malformations of cortical development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Marked gene: KIF1BP as ready
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name KIFBP.
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Gene: kif1bp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2694 KIF1BP Zornitza Stark Tag new gene name tag was added to gene: KIF1BP.
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Gene: slc6a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2694 SLC6A1 Zornitza Stark Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, MIM#616421
Intellectual disability syndromic and non-syndromic v0.2693 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to
Intellectual disability syndromic and non-syndromic v0.2692 SLC6A1 Zornitza Stark Mode of inheritance for gene: SLC6A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2691 SLC6A1 Zornitza Stark reviewed gene: SLC6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29315614; Phenotypes: Myoclonic-atonic epilepsy, MIM#616421; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Marked gene: GATM as ready
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Phenotypes for gene: GATM were changed from to Cerebral creatine deficiency syndrome 3, MIM# 612718
Intellectual disability syndromic and non-syndromic v0.2690 GATM Zornitza Stark Publications for gene: GATM were set to
Intellectual disability syndromic and non-syndromic v0.2689 GATM Zornitza Stark Mode of inheritance for gene: GATM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2688 GATM Zornitza Stark reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12468279, 20682460, 22386973; Phenotypes: Cerebral creatine deficiency syndrome 3, MIM# 612718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Marked gene: PSMB1 as ready
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Classified gene: PSMB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Gene: psmb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2687 PSMB1 Zornitza Stark gene: PSMB1 was added
gene: PSMB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMB1 were set to 32129449
Phenotypes for gene: PSMB1 were set to Intellectual disability; microcephaly
Review for gene: PSMB1 was set to AMBER
Added comment: Two siblings reported with a homozygous missense variant in this gene; supportive experimental evidence including zebrafish model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2686 C16orf62 Zornitza Stark changed review comment from: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list; to: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475;31712251).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2686 C16orf62 Zornitza Stark Publications for gene: C16orf62 were set to 25434475; 31712251
Intellectual disability syndromic and non-syndromic v0.2685 C16orf62 Zornitza Stark Publications for gene: C16orf62 were set to 25434475
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark edited their review of gene: C16orf62: Changed publications: 25434475, 31712251
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Tag new gene name tag was added to gene: C16orf62.
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Classified gene: C16orf62 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2684 C16orf62 Zornitza Stark Gene: c16orf62 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2683 C16orf62 Zornitza Stark gene: C16orf62 was added
gene: C16orf62 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 25434475
Phenotypes for gene: C16orf62 were set to 3C/Ritscher-Schinzel-like syndrome
Review for gene: C16orf62 was set to AMBER
Added comment: HGNC approved name: VPS35L. Two variants have been reported as compound heterozygotes in two sibs with features of 3C/Ritscher-Schinzel syndrome. Functional studies show that loss of VPS35L function results in impared autophagy and VPS35L knockout mouse resulted in early embrionic lethality (PMID 25434475).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Marked gene: PPP1CB as ready
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Gene: ppp1cb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2682 PPP1CB Zornitza Stark Phenotypes for gene: PPP1CB were changed from to Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506
Intellectual disability syndromic and non-syndromic v0.2681 PPP1CB Zornitza Stark Publications for gene: PPP1CB were set to
Intellectual disability syndromic and non-syndromic v0.2680 PPP1CB Zornitza Stark Mode of inheritance for gene: PPP1CB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2679 PPP1CB Zornitza Stark reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: None; Publications: 32476286, 28211982, 27264673, 27681385, 27868344; Phenotypes: Noonan syndrome-like disorder with loose anlagen hair 2, OMIM # 617506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark Marked gene: RBL2 as ready
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark Gene: rbl2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2679 RBL2 Zornitza Stark gene: RBL2 was added
gene: RBL2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to 32105419; 9806916
Phenotypes for gene: RBL2 were set to Intellectual disability
Review for gene: RBL2 was set to RED
Added comment: Single family reported with pair of affected siblings. Supportive mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Marked gene: GRM7 as ready
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Classified gene: GRM7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Gene: grm7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2677 GRM7 Zornitza Stark gene: GRM7 was added
gene: GRM7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 32286009; 32248644
Phenotypes for gene: GRM7 were set to Epilepsy, microcephaly, developmental delay
Review for gene: GRM7 was set to GREEN
Added comment: Eleven individuals from six families reported, three different homozygous variants (two missense, one LoF). Developmental delay, neonatal‐ or infantile‐onset epilepsy, and microcephaly were universal. Supportive mouse model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2676 DSCR3 Zornitza Stark Marked gene: DSCR3 as ready
Intellectual disability syndromic and non-syndromic v0.2676 DSCR3 Zornitza Stark Gene: dscr3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2676 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, no OMIM# yet to Epileptic encephalopathy, intellectual disability, no OMIM# yet
Intellectual disability syndromic and non-syndromic v0.2675 OTUD7A Zornitza Stark Publications for gene: OTUD7A were set to PMID: 31997314
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark reviewed gene: OTUD7A: Rating: RED; Mode of pathogenicity: None; Publications: 29395075, 29395074; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark Marked gene: OTUD7A as ready
Intellectual disability syndromic and non-syndromic v0.2674 OTUD7A Zornitza Stark Gene: otud7a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Marked gene: GATAD2B as ready
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Gene: gatad2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2674 GATAD2B Zornitza Stark Phenotypes for gene: GATAD2B were changed from to Mental retardation, autosomal dominant 18, OMIM # 615074
Intellectual disability syndromic and non-syndromic v0.2673 GATAD2B Zornitza Stark Publications for gene: GATAD2B were set to
Intellectual disability syndromic and non-syndromic v0.2672 GATAD2B Zornitza Stark Mode of inheritance for gene: GATAD2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Marked gene: KMT2D as ready
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Gene: kmt2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome to Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome to Kabuki syndrome 1, MIM# 147920; KMT2D-associated syndrome
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark Deleted their review
Intellectual disability syndromic and non-syndromic v0.2670 KMT2D Zornitza Stark Phenotypes for gene: KMT2D were changed from to Kabuki syndrome 1, MIM# 147920; KMT2D-associated neurodevelopmental syndrome
Intellectual disability syndromic and non-syndromic v0.2669 KMT2D Zornitza Stark Publications for gene: KMT2D were set to
Intellectual disability syndromic and non-syndromic v0.2668 KMT2D Zornitza Stark Mode of inheritance for gene: KMT2D was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2667 KMT2D Zornitza Stark reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kabuki syndrome 1, MIM# 147920, KMT2D-associated neurodevelopmental syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2667 COG4 Zornitza Stark Publications for gene: COG4 were set to
Intellectual disability syndromic and non-syndromic v0.2666 COG4 Zornitza Stark Mode of inheritance for gene: COG4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2665 COG4 Zornitza Stark Deleted their review
Intellectual disability syndromic and non-syndromic v0.2665 COG4 Zornitza Stark reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31949312, 30290151, 19494034, 21185756; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2665 DSCR3 Chirag Patel gene: DSCR3 was added
gene: DSCR3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DSCR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DSCR3 were set to PMID: 31845315
Phenotypes for gene: DSCR3 were set to Intellectual disability, no OMIM # yet
Review for gene: DSCR3 was set to RED
Added comment: 1 family/2 cousins with cognitive impairment, growth failure, skeletal abnormalities, and distinctive facial features. Both shared the homozygous nonsense variant c.178G>T (p.Glu60*) in the VPS26C gene. This gene encodes VPS26C, a member of the retriever integral membrane protein recycling pathway. The nature of the variant which is predicted to result in loss‐of‐function, expression studies revealing significant reduction in the mutant transcript, and the co‐segregation of the homozygous variant with the phenotype in two affected individuals.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2664 OTUD7A Chirag Patel gene: OTUD7A was added
gene: OTUD7A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: OTUD7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTUD7A were set to PMID: 31997314
Phenotypes for gene: OTUD7A were set to Epileptic encephalopathy, no OMIM# yet
Review for gene: OTUD7A was set to RED
Added comment: One patient with severe global developmental delay, language impairment and epileptic encephalopathy. Homozygous OTUD7A missense variant (c.697C>T, p.Leu233Phe), predicted to alter an ultraconserved amino acid, lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. We provide evidence that biallelic pathogenic OTUD7A variation is linked to early‐onset epileptic encephalopathy and proteasome dysfunction. Gene lies in the chromosome 15q13.3 region. Heterozygous microdeletions of chromosome 15q13.3 show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2663 GATAD2B Chirag Patel reviewed gene: GATAD2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949314; Phenotypes: Mental retardation, autosomal dominant 18, OMIM # 615074; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2663 KMT2D Chirag Patel changed review comment from: KMT2D missense variants located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from Kabuki syndrome, through a dominant negative mechanism.; to: KMT2D missense variants located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from Kabuki syndrome, through a dominant negative mechanism.
- 7 unrelated families with choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability.
Intellectual disability syndromic and non-syndromic v0.2663 KMT2D Chirag Patel reviewed gene: KMT2D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949313; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2663 COG4 Chirag Patel reviewed gene: COG4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31949312, 30290151; Phenotypes: Saul-Wilson syndrome, OMIM #618150, Congenital disorder of glycosylation, type IIj, OMIM #613489; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Marked gene: ARL13B as ready
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Gene: arl13b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2663 ARL13B Zornitza Stark Phenotypes for gene: ARL13B were changed from to Joubert syndrome 8, MIM# 612291
Intellectual disability syndromic and non-syndromic v0.2662 ARL13B Zornitza Stark Publications for gene: ARL13B were set to
Intellectual disability syndromic and non-syndromic v0.2661 ARL13B Zornitza Stark Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2660 ARL13B Zornitza Stark reviewed gene: ARL13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18674751, 25138100, 26092869, 27894351, 29255182, 17488627; Phenotypes: Joubert syndrome 8, MIM# 612291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Marked gene: TTC5 as ready
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Classified gene: TTC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2660 TTC5 Zornitza Stark Gene: ttc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2659 TTC5 Konstantinos Varvagiannis gene: TTC5 was added
gene: TTC5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TTC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC5 were set to 29302074; 32439809
Phenotypes for gene: TTC5 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Microcephaly; Abnormality of the face; Behavioral abnormality; Abnormality of the genitourinary system
Penetrance for gene: TTC5 were set to Complete
Review for gene: TTC5 was set to GREEN
Added comment: Hu et al (2019 - PMID: 29302074) reported briefly on 3 individuals from 2 consanguineous families (from Turkey and Iran) with biallelic TTC5 variants. Features included DD (3/3), ID (severe in 2/2 with relevant age), microcephaly (3/3), brain abnormalities, etc. A nonsense and a variant affecting splice site were identified by WES/WGS.

---

In a recent report, Rasheed et al (2020 - PMID: 32439809) report on the phenotype of 8 individuals - belonging to 5 consanguineous families - all 8 harboring homozygous TTC5 mutations.

Frequent features included hypotonia (6/8), motor and speech delay, moderate to severe ID (10/10 of relevant age - inclusion of less severely affected subjects was not considered by study design), brain MRI abnormalities (8/8). Other findings included microcephaly in some (6/11), behavioral abnormalities in few (autistic behavior in 2/8, aggression in 2/8), genitourinary anomalies (2/8), seizures (1/11). Facial phenotype incl. thin V-shaped upper lip, low-set ears (in most) and/or additional features.

TTC5 encodes a 440 aa protein, functioning as a scaffold to stabilise p300-JMY interactions. Apart from this role in nucleus, it has functions in the cytoplasm (inhibiting actin nucleataion, autophagosome formation, etc).

The gene has ubiquitous expression, highest in brain.

All variants were identified following WES - as the best candidates - in affected individuals with compatible Sanger studies in all affected family members and carrier parents.

2 missense and 2 nonsense variants were identified with the 2 missense SNVs localizing within TPR domains. qRT-PCR studies for a nonsense variant localizing 19 nt before the last exon, revealed fourfold decreased expression in affected individuals compared to carriers.

Families from Egypt shared a homozygous ~6.3 Mb haplotype block spanning TTC5, suggesting that p.(Arg263Ter) is likely a founder mutation.

The authors underscore some phenotypic (though not facial) similarities with Rubinstein-Taybi syndrome 2 due to EP300 mutations (in line with the role of TTC5).

Biallelic variants in genes encoding other members of the TTC family (containing a TPR motif), e.g. TTC8 or TTC15 cause disorders with neurologic manifestations (and DD/ID).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Marked gene: SOX6 as ready
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Added comment: Comment when marking as ready: Most individuals had ID, ranging from mild to severe.
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Classified gene: SOX6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2659 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome. Paper says 19 individuals from 17 families. 12 were de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio changed review comment from: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature; to: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me (paper says 19 individuals from 17 families). 12 were de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2658 SOX6 Paul De Fazio gene: SOX6 was added
gene: SOX6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX6 were set to 32442410
Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas
Review for gene: SOX6 was set to GREEN
Added comment: 6 LoF, 4 missense, and 6 intragenic deletion variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2658 HIST1H4J Sue White Classified gene: HIST1H4J as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2658 HIST1H4J Sue White Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White Marked gene: HIST1H4J as ready
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White Gene: hist1h4j has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2657 HIST1H4J Sue White gene: HIST1H4J was added
gene: HIST1H4J was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HIST1H4J was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIST1H4J were set to 31804630
Phenotypes for gene: HIST1H4J were set to microcephaly; intellectual disability; dysmorphic features
Penetrance for gene: HIST1H4J were set to Complete
Review for gene: HIST1H4J was set to AMBER
Added comment: single case report but with functional evidence in zebrafish and phenotypic similarity to other HIST1H4C phenotype
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2656 ADAM22 Zornitza Stark Classified gene: ADAM22 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2656 ADAM22 Zornitza Stark Gene: adam22 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 ADAM22 Zornitza Stark Marked gene: ADAM22 as ready
Intellectual disability syndromic and non-syndromic v0.2655 ADAM22 Zornitza Stark Gene: adam22 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RAX Zornitza Stark Marked gene: RAX as ready
Intellectual disability syndromic and non-syndromic v0.2655 RAX Zornitza Stark Gene: rax has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 TUBA8 Zornitza Stark Marked gene: TUBA8 as ready
Intellectual disability syndromic and non-syndromic v0.2655 TUBA8 Zornitza Stark Gene: tuba8 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 XIST Zornitza Stark Marked gene: XIST as ready
Intellectual disability syndromic and non-syndromic v0.2655 XIST Zornitza Stark Gene: xist has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 WFS1 Zornitza Stark Marked gene: WFS1 as ready
Intellectual disability syndromic and non-syndromic v0.2655 WFS1 Zornitza Stark Gene: wfs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Marked gene: RBM10 as ready
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Gene: rbm10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2655 RBM10 Zornitza Stark Phenotypes for gene: RBM10 were changed from to TARP syndrome, 311900 (3), X-linked recessive
Intellectual disability syndromic and non-syndromic v0.2654 RBM10 Zornitza Stark Publications for gene: RBM10 were set to
Intellectual disability syndromic and non-syndromic v0.2653 RBM10 Zornitza Stark Mode of inheritance for gene: RBM10 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2652 RBM10 Michelle Torres reviewed gene: RBM10: Rating: GREEN; Mode of pathogenicity: None; Publications: 24259342, 24000153, 30462380; Phenotypes: TARP syndrome, 311900 (3), X-linked recessive; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.2652 MADD Zornitza Stark Marked gene: MADD as ready
Intellectual disability syndromic and non-syndromic v0.2652 MADD Zornitza Stark Gene: madd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2652 MADD Zornitza Stark Phenotypes for gene: MADD were changed from to intellectual disability
Intellectual disability syndromic and non-syndromic v0.2651 MADD Zornitza Stark Publications for gene: MADD were set to
Intellectual disability syndromic and non-syndromic v0.2650 MADD Zornitza Stark Mode of inheritance for gene: MADD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2649 DHX30 Zornitza Stark Marked gene: DHX30 as ready
Intellectual disability syndromic and non-syndromic v0.2649 DHX30 Zornitza Stark Gene: dhx30 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2649 DHX30 Zornitza Stark Phenotypes for gene: DHX30 were changed from to Neurodevelopmental disorder with severe motor impairment and absent language, MIM#617804
Intellectual disability syndromic and non-syndromic v0.2648 DHX30 Zornitza Stark Publications for gene: DHX30 were set to
Intellectual disability syndromic and non-syndromic v0.2647 DHX30 Zornitza Stark Mode of inheritance for gene: DHX30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2646 DHX30 Zornitza Stark reviewed gene: DHX30: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100085; Phenotypes: Neurodevelopmental disorder with severe motor impairment and absent language, MIM#617804; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2646 JARID2 Zornitza Stark Marked gene: JARID2 as ready
Intellectual disability syndromic and non-syndromic v0.2646 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2646 JARID2 Zornitza Stark Classified gene: JARID2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2646 JARID2 Zornitza Stark Gene: jarid2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2645 JARID2 Zornitza Stark gene: JARID2 was added
gene: JARID2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: JARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JARID2 were set to 23294540
Phenotypes for gene: JARID2 were set to Intellectual disability
Review for gene: JARID2 was set to AMBER
Added comment: Emerging evidence, mostly based on CNV data to date.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2644 TRIP12 Zornitza Stark Marked gene: TRIP12 as ready
Intellectual disability syndromic and non-syndromic v0.2644 TRIP12 Zornitza Stark Gene: trip12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2644 TRIP12 Zornitza Stark Phenotypes for gene: TRIP12 were changed from to Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752
Intellectual disability syndromic and non-syndromic v0.2643 TRIP12 Zornitza Stark Publications for gene: TRIP12 were set to 27848077; 28251352
Intellectual disability syndromic and non-syndromic v0.2643 TRIP12 Zornitza Stark Publications for gene: TRIP12 were set to
Intellectual disability syndromic and non-syndromic v0.2642 TRIP12 Zornitza Stark Mode of inheritance for gene: TRIP12 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2641 TRIP12 Chern Lim reviewed gene: TRIP12: Rating: GREEN; Mode of pathogenicity: None; Publications: 27848077, 28251352; Phenotypes: Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.2641 B9D1 Zornitza Stark Classified gene: B9D1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2641 B9D1 Zornitza Stark Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2640 B9D1 Zornitza Stark changed review comment from: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype.; to: Two unrelated individuals with JS and bi-allelic variants in this gene, plus one individual with a more severe Meckel phenotype described. Intellectual disability is part of the phenotype. However note that in Meckel individual one of the variants identified is a multi-gene deletion and in addition a likely path CEP290 variant also reported.
Intellectual disability syndromic and non-syndromic v0.2640 B9D1 Zornitza Stark edited their review of gene: B9D1: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2640 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Intellectual disability syndromic and non-syndromic v0.2640 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2640 PACS1 Zornitza Stark Phenotypes for gene: PACS1 were changed from to Schuurs-Hoeijmakers syndrome (MIM# 615009)
Intellectual disability syndromic and non-syndromic v0.2639 PACS1 Zornitza Stark Publications for gene: PACS1 were set to
Intellectual disability syndromic and non-syndromic v0.2638 PACS1 Zornitza Stark Mode of inheritance for gene: PACS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2637 PACS1 Zornitza Stark reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26842493, 23159249; Phenotypes: Schuurs-Hoeijmakers syndrome (MIM# 615009); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2637 IQSEC3 Zornitza Stark Phenotypes for gene: IQSEC3 were changed from Intellectual disability to Intellectual disability; Fetal akinesia
Intellectual disability syndromic and non-syndromic v0.2636 IQSEC3 Zornitza Stark Publications for gene: IQSEC3 were set to 31130284
Intellectual disability syndromic and non-syndromic v0.2635 IQSEC3 Elena Savva reviewed gene: IQSEC3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32049026, 31130284, 31680123; Phenotypes: Intellectual disability, Fetal akinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Marked gene: PRKD1 as ready
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Gene: prkd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2635 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
Intellectual disability syndromic and non-syndromic v0.2634 PRKD1 Zornitza Stark Publications for gene: PRKD1 were set to
Intellectual disability syndromic and non-syndromic v0.2633 PRKD1 Zornitza Stark Mode of inheritance for gene: PRKD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2632 PRKD1 Zornitza Stark reviewed gene: PRKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27479907; Phenotypes: Congenital heart defects and ectodermal dysplasia, 617364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Added comment: Comment when marking as ready: Upgrade to Green in view of new publication reporting 9 additional individuals.
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Classified gene: NR4A2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2632 NR4A2 Zornitza Stark Gene: nr4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2631 NR4A2 Konstantinos Varvagiannis reviewed gene: NR4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1038/s41436-020-0815-4, 31428396, 29770430, 30504930, 28544326, 27569545, 23554088, 28135719, 27479843, 25363768; Phenotypes: Generalized hypotonia, Global developmental delay, Intellectual disability, Seizures, Behavioral abnormality, Abnormality of movement, Joint hypermobility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Marked gene: CUL3 as ready
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2631 CUL3 Zornitza Stark Phenotypes for gene: CUL3 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496 to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate
Intellectual disability syndromic and non-syndromic v0.2630 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2630 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2629 CUL3 Konstantinos Varvagiannis gene: CUL3 was added
gene: CUL3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CUL3 were set to 32341456
Phenotypes for gene: CUL3 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of cardiovascular system morphology; Abnormality of the palate; Pseudohypoaldosteronism, type IIE - MIM #614496
Penetrance for gene: CUL3 were set to unknown
Review for gene: CUL3 was set to GREEN
Added comment: Please consider inclusion with amber / green rating.
--
Nakashima et al (2020 - PMID:32341456) provide clinical details on 3 unrelated individuals with de novo CUL3 variants.

Features included DD, variable degrees of ID (P1: severe, P3: mild, P2: NA although he displayed motor and severe speech and language delay and had severe learning difficulties). Two out of three had intractable seizures (onset 2 - 6 months). One presented with congenital heart defects (ASD, PV stenosis) and another submucosal palatoschisis/bifid uvula. There were no facial dysmorphisms reported.

CUL3 encodes Cullin-3, a core piece of the E3 ubiquitin ligase complex, thus playing a role in the ubiquitin-proteasome system. [ https://ghr.nlm.nih.gov/gene/CUL3 ]. Germline variants in some other Cullin family genes (eg. CUL4B, CUL7) cause disorders with ID as a feature.

The 3 individuals reported by Nakashima had variable previous investigations (karyotype, CMA, metabolic testing) which were non-diagnostic. Singleton or trio exome sequencing identified 2 frameshift and 1 missense variant (NM_003590.4:c.854T>C / p.Val285Ala), further confirmed with Sanger sequencing. De novo occurrence was confirmed by analysis of microsatellite markers in an individual with singleton ES.

While the frameshift variants were presumed to lead to NMD (not studied), studies in HEK293T cells suggested that the Val285Ala reduced binding ability with KEAP1, possibly leading to instability of the Cullin-RING ligase (CRL) complex and impairment of the ubiquitin-proteasome system.

In OMIM, the phenotype associated with heterozygous CUL3 mutations is Pseudohypoaldosteronism type IIE (PHA2E - # 614496). As OMIM and Nakashima et al comment, PHA2E-associated variants are clustered around exon 9, most lead to skipping of exon 9 and produce an in-frame deletion of 57 aa in the cullin homology domain. Few (probably 3) missense variants in exon 9 have also been reported. Individuals with PHA2E do not display DD/ID and conversely individuals with NDD did not display features of PHA2E.

Nakashima et al summarize the phenotypes associated with 12 further de novo CUL3 variants in the literature with most pLOF ones detected in individuals with autism and/or developmental disorders and in few cases with congenital heart disease. Few additional missense variants and a stoploss one have been reported in individuals with NDD and one in SCZ.

Heterozygous Cul3 (/tissue-specific) deletion in mice resulted in autism-like behavior. Cul3 deficient mice also demonstrated NMDAR hypofunction and decreased spine density. [PMIDs cited : 31455858, 31780330]

Overall haploinsufficiency is favored as the underlying mechanism of variants associated with NDD. Nakashima et al comment that the pathogenesis of missense variants remains unknown and/or that a dominant-negative effect on CRL may be possible.

Studies on larger cohorts reporting on individuals with relevant phenotypes due to de novo CUL3 variants (eg. DDD study - PMID: 28135719, Lelieveld et al - PMID: 27479843), are summarized in denovo-db (after filtering for coding variants):

http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=cul3

Overall, this gene can be considered for inclusion in the ID (amber/green), epilepsy (amber) and/or ASD panels.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2629 ADAM22 Zornitza Stark gene: ADAM22 was added
gene: ADAM22 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: ADAM22 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAM22 were set to 27066583; 30237576
Phenotypes for gene: ADAM22 were set to Epileptic encephalopathy, early infantile, 61, MIM# 617933
Review for gene: ADAM22 was set to AMBER
Added comment: Two families reported; the second one as part of a large consanguineous cohort.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Marked gene: UGDH as ready
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Classified gene: UGDH as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2628 UGDH Zornitza Stark Gene: ugdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2627 UGDH Konstantinos Varvagiannis gene: UGDH was added
gene: UGDH was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGDH were set to 32001716
Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792
Penetrance for gene: UGDH were set to Complete
Review for gene: UGDH was set to GREEN
Added comment: Hengel et al (2020 - PMID: 32001716) report on 36 individuals with biallelic UGDH pathogenic variants.

The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever.

Affected subjects were tested by exome sequencing and UGDH variants were the only/best candidates for the phenotype following also segregation studies. Many were compound heterozygous or homozygous (~6 families were consanguineous) for missense variants and few were compound heterozygous for missense and pLoF variants. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode.

UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate [OMIM].

Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate).

Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ.

Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Marked gene: SPTBN4 as ready
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Classified gene: SPTBN4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2627 SPTBN4 Zornitza Stark Gene: sptbn4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Marked gene: YIF1B as ready
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Classified gene: YIF1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2626 YIF1B Zornitza Stark Gene: yif1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2625 YIF1B Konstantinos Varvagiannis gene: YIF1B was added
gene: YIF1B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Penetrance for gene: YIF1B were set to Complete
Review for gene: YIF1B was set to GREEN
Added comment: AlMuhaizea et al (2020 - PMID: 32006098) report on the phenotype of 6 individuals (from 5 families) with biallelic YIF1B truncating variants.

Affected subjects presented hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID (as evident from best motor/language milestones achieved - Table S1) as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Variable initial investigations were performed including SNP CMA, MECP2, microcephaly / neurotransmitter disorders gene panel testing did not reveal P/LP variants.

YIF1B variants were identified in 3 families within ROH. Following exome sequencing, affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

YIF1B encodes an intracellular transmembrane protein.

It has been previously demonstrated that - similarly to other proteins of the Yip family being implicated in intracellular traffic between the Golgi - Yif1B is involved in the anterograde traffic pathway. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). The rat ortholog interacts with serotonin receptor 1 (5-HT1AR) with colocalization of Yif1BB and 5-HT1AR in intermediate compartment vesicles and involvement of the former in intracellular trafficing/modulation of 5-HT1AR transport to dendrites (PMID cited: 18685031).

Available mRNA and protein expression data (Protein Atlas) suggest that the gene is widely expressed in all tissues incl. neuronal cells. Immunochemistry data from the Human Brain Atlas also suggest that YIF1B is found in vesicles and localized to the Golgi apparatus. Immunohistochemistry in normal human brain tissue (cerebral cortex) demonstrated labeling of neuronal cells (Human Protein Atlas).

Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.

Please consider inclusion in other panels that may be relevant (e.g. microcephaly, etc).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2625 SPTBN4 Konstantinos Varvagiannis reviewed gene: SPTBN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28540413, 28940097, 29861105, 31230720, 31857255; Phenotypes: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2625 TNRC6B Zornitza Stark Phenotypes for gene: TNRC6B were changed from to Global developmental delay; Intellectual disability; Autistic behavior
Intellectual disability syndromic and non-syndromic v0.2624 TNRC6B Zornitza Stark Publications for gene: TNRC6B were set to
Intellectual disability syndromic and non-syndromic v0.2623 TNRC6B Zornitza Stark Mode of inheritance for gene: TNRC6B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2622 TNRC6B Zornitza Stark Classified gene: TNRC6B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2622 TNRC6B Zornitza Stark Gene: tnrc6b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Marked gene: CDC42BPB as ready
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2621 CDC42BPB Zornitza Stark Mode of inheritance for gene: CDC42BPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2620 CDC42BPB Zornitza Stark Classified gene: CDC42BPB as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2620 CDC42BPB Zornitza Stark Gene: cdc42bpb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2619 TNRC6B Konstantinos Varvagiannis reviewed gene: TNRC6B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32152250, 28135719, 25363768, 27479843, 28959963, 25228304; Phenotypes: Global developmental delay, Intellectual disability, Autistic behavior; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2619 CDC42BPB Konstantinos Varvagiannis gene: CDC42BPB was added
gene: CDC42BPB was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDC42BPB were set to 32031333
Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality
Penetrance for gene: CDC42BPB were set to unknown
Review for gene: CDC42BPB was set to GREEN
Added comment: Chilton et al (2020 - PMID: 32031333) report on 14 individuals with missense and loss-of-function CDC42BPB variants.

Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc.

All individuals had non-diagnostic prior genetic testing (incl. CMA, FMR1, MECP2, Angelman/Prader-Willi methylation studies, autism gene panel - suggesting relevance to the current panel) or metabolic testing.

Variants were identified following clinical exome sequencing with Sanger confirmation. Most occurred as de novo events (11/14) while inheritance was not available for few (3/14). Missense variants did not display (particular) clustering.

Almost all variants were absent from gnomAD and were predicted to be deleterious in silico (among others almost all had CADD scores >25).

As the authors comment, CDC42BPB encodes myotonic dystrophy-related Cdc42-binding kinase β (MRCKβ) a serine/threonine protein kinase playing a role in regulation of cytoskeletal reorganization and cell migration in nonmuscle cells (through phosporylation of MLC2).

Previous studies have demonstrated that it is ubiquitously expressed with prenatal brain expression.

The gene appears to be intolerant to pLoF (pLI of 1) as well as to missense variants (Z-score of 3.66).

CDC42BPB is a downstream effector of CDC42. Mutations of the latter cause Takenouchi-Kosaki syndrome with DD/ID and some further overlapping features (with CDC42BPB-associated phenotypes).

Homozygous Cdc42bpb KO in mouse appears to be nonviable (MGI:2136459). Loss of gek in the eyes of Drosophila results in disrupted growth cone targeting to the lamina (gek is the fly CDC42BPB ortholog).

Please consider inclusion with amber / green rating in the ID panel (>=4 relevant individuals / variants) and other panels (e.g. for epilepsy, ASD).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2619 ARMC9 Zornitza Stark Marked gene: ARMC9 as ready
Intellectual disability syndromic and non-syndromic v0.2619 ARMC9 Zornitza Stark Gene: armc9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2619 ARMC9 Zornitza Stark Phenotypes for gene: ARMC9 were changed from Joubert syndrome 30, MIM# 617622 to Joubert syndrome 30, MIM# 617622
Intellectual disability syndromic and non-syndromic v0.2618 ARMC9 Zornitza Stark Phenotypes for gene: ARMC9 were changed from to Joubert syndrome 30, MIM# 617622
Intellectual disability syndromic and non-syndromic v0.2617 ARMC9 Zornitza Stark Publications for gene: ARMC9 were set to
Intellectual disability syndromic and non-syndromic v0.2616 ARMC9 Zornitza Stark Mode of inheritance for gene: ARMC9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2615 ARMC9 Zornitza Stark reviewed gene: ARMC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28625504; Phenotypes: Joubert syndrome 30, MIM# 617622; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2615 DARS Zornitza Stark Marked gene: DARS as ready
Intellectual disability syndromic and non-syndromic v0.2615 DARS Zornitza Stark Gene: dars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2615 DARS Zornitza Stark Phenotypes for gene: DARS were changed from to Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281
Intellectual disability syndromic and non-syndromic v0.2614 DARS Zornitza Stark Publications for gene: DARS were set to
Intellectual disability syndromic and non-syndromic v0.2613 DARS Zornitza Stark Mode of inheritance for gene: DARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2612 DARS Zornitza Stark Tag new gene name tag was added to gene: DARS.
Intellectual disability syndromic and non-syndromic v0.2612 DARS Zornitza Stark reviewed gene: DARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 25527264, 23643384; Phenotypes: Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2612 ARID1B Zornitza Stark Marked gene: ARID1B as ready
Intellectual disability syndromic and non-syndromic v0.2612 ARID1B Zornitza Stark Gene: arid1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2612 ARID1B Zornitza Stark Phenotypes for gene: ARID1B were changed from to Coffin-Siris syndrome 1, MIM 135900
Intellectual disability syndromic and non-syndromic v0.2611 ARID1B Zornitza Stark Publications for gene: ARID1B were set to
Intellectual disability syndromic and non-syndromic v0.2610 ARID1B Zornitza Stark Mode of inheritance for gene: ARID1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2609 ARID1B Teresa Zhao reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25674384, 30349098, 26506440; Phenotypes: Coffin-Siris syndrome 1, MIM 135900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2609 EMX2 Zornitza Stark Tag disputed tag was added to gene: EMX2.
Intellectual disability syndromic and non-syndromic v0.2609 EMX2 Zornitza Stark Marked gene: EMX2 as ready
Intellectual disability syndromic and non-syndromic v0.2609 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2609 EMX2 Zornitza Stark Phenotypes for gene: EMX2 were changed from to Schizencephaly, MIM# 269160
Intellectual disability syndromic and non-syndromic v0.2608 EMX2 Zornitza Stark Publications for gene: EMX2 were set to
Intellectual disability syndromic and non-syndromic v0.2607 EMX2 Zornitza Stark Mode of inheritance for gene: EMX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2606 EMX2 Zornitza Stark Classified gene: EMX2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2606 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2605 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 8528262, 9359037, 9153481, 9153481, 18409201; Phenotypes: Schizencephaly, MIM# 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2605 ATAD3A Zornitza Stark Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome, MIM# 617183 to Harel-Yoon syndrome, MIM# 617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810
Intellectual disability syndromic and non-syndromic v0.2604 ATAD3A Zornitza Stark Publications for gene: ATAD3A were set to 27640307; 32004445
Intellectual disability syndromic and non-syndromic v0.2603 ATAD3A Zornitza Stark Mode of pathogenicity for gene: ATAD3A was changed from to Other
Intellectual disability syndromic and non-syndromic v0.2602 ATAD3A Zornitza Stark edited their review of gene: ATAD3A: Added comment: Note mode of pathogenicity includes:
i) bi-allelic missense and nonsense variants and bi-allelic deletions that create an ATAD3B/ATAD3A fusion gene under the lowly expressed ATAD3B promoter
ii) monoallelic dominant-negative missense variants (either de novo or inherited) and de novo monoallelic duplications creating a dominant negative ATAD3A/ATAD3C fusion gene; Changed publications: 27640307, 32004445, 28549128; Changed phenotypes: Harel-Yoon syndrome, MIM# 617183, Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (PHRINL SYNDROME) 618810
Intellectual disability syndromic and non-syndromic v0.2602 MN1 Zornitza Stark Phenotypes for gene: MN1 were changed from Intellectual disability; dysmophic features; rhombencephalosynapsis to CEBALID syndrome, MIM#618774; Intellectual disability; dysmophic features; rhombencephalosynapsis
Intellectual disability syndromic and non-syndromic v0.2601 MN1 Zornitza Stark Mode of inheritance for gene: MN1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2600 MN1 Zornitza Stark edited their review of gene: MN1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2600 VPS51 Zornitza Stark Marked gene: VPS51 as ready
Intellectual disability syndromic and non-syndromic v0.2600 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2600 VPS51 Zornitza Stark Classified gene: VPS51 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2600 VPS51 Zornitza Stark Gene: vps51 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2599 VPS51 Zornitza Stark gene: VPS51 was added
gene: VPS51 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, MIM# 618606
Review for gene: VPS51 was set to AMBER
Added comment: Two families reported with bi-allelic variants in this gene and global developmental delay, impaired intellectual development with absent speech, microcephaly, and progressive atrophy of the cerebellar vermis and brainstem. Additional features, including seizures and visual impairment, are variable.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2598 MN1 Chern Lim reviewed gene: MN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CEBALID syndrome, MIM#618774; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2598 CDK19 Zornitza Stark Marked gene: CDK19 as ready
Intellectual disability syndromic and non-syndromic v0.2598 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2598 CDK19 Zornitza Stark Classified gene: CDK19 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2598 CDK19 Zornitza Stark Gene: cdk19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2597 CDK19 Zornitza Stark gene: CDK19 was added
gene: CDK19 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDK19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK19 were set to 32330417
Phenotypes for gene: CDK19 were set to Intellectual disability; epileptic encephalopathy
Review for gene: CDK19 was set to GREEN
Added comment: Three unrelated individuals with de novo missense variants reported, and intellectual disability/epileptic encephalopathy. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2596 PTPN23 Zornitza Stark Marked gene: PTPN23 as ready
Intellectual disability syndromic and non-syndromic v0.2596 PTPN23 Zornitza Stark Gene: ptpn23 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2596 PTPN23 Zornitza Stark Mode of inheritance for gene: PTPN23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2595 PTPN23 Zornitza Stark Publications for gene: PTPN23 were set to
Intellectual disability syndromic and non-syndromic v0.2594 PTPN23 Zornitza Stark Phenotypes for gene: PTPN23 were changed from to Intellectual disability; brain abnormalities; seizures; optic atrophy; microcephaly
Intellectual disability syndromic and non-syndromic v0.2593 PTPN23 Zornitza Stark reviewed gene: PTPN23: Rating: GREEN; Mode of pathogenicity: None; Publications: 31395947; Phenotypes: Intellectual disability, brain abnormalities, seizures, optic atrophy, microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2593 PHF21A Zornitza Stark Phenotypes for gene: PHF21A were changed from no OMIM number yet. to Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, MIM# 618725
Intellectual disability syndromic and non-syndromic v0.2592 PHF21A Zornitza Stark edited their review of gene: PHF21A: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.2592 PHF21A Zornitza Stark reviewed gene: PHF21A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures 618725; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2592 CYFIP2 Zornitza Stark Phenotypes for gene: CYFIP2 were changed from Epileptic encephalopathy, early infantile, 65, MIM#618008 to Epileptic encephalopathy, early infantile, 65, MIM#618008; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.2591 CYFIP2 Zornitza Stark Publications for gene: CYFIP2 were set to 29534297
Intellectual disability syndromic and non-syndromic v0.2590 CYFIP2 Zornitza Stark edited their review of gene: CYFIP2: Added comment: Further 12 independent patients with a variety of de novo variants in CYFIP2 reported with eight distinct de novo variants and a shared phenotype of intellectual disability, seizures, and muscular hypotonia. Seven different missense variants detected, of which two occurred recurrently (p.(Arg87Cys) and p.(Ile664Met)). Preliminary genotype–phenotype correlation indicates a profound phenotype in p.Arg87 substitutions and a more variable phenotype in other alterations.; Changed publications: 29534297, 30664714; Changed phenotypes: Epileptic encephalopathy, early infantile, 65, MIM#618008, Intellectual disability
Intellectual disability syndromic and non-syndromic v0.2590 CEP55 Zornitza Stark Marked gene: CEP55 as ready
Intellectual disability syndromic and non-syndromic v0.2590 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2590 CEP55 Zornitza Stark Classified gene: CEP55 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2590 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2589 CEP55 Zornitza Stark gene: CEP55 was added
gene: CEP55 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP55 were set to 32100459
Phenotypes for gene: CEP55 were set to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500; Microcephaly; Intellectual disability
Review for gene: CEP55 was set to GREEN
Added comment: Homozygous nonsense variants in CEP55 are associated with a lethal condition characterized by multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly (MARCH syndrome) also known as Meckel-like syndrome. New report of seven living individuals from five families with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all had a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings were homozygous for a consensus splice site variant near the end of the gene. These affected girls all had severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. This series suggests that individuals with compound heterozygosity for nonsense and missense variants in CEP55 have a different viable phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2588 LRRC32 Zornitza Stark Marked gene: LRRC32 as ready
Intellectual disability syndromic and non-syndromic v0.2588 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2588 LRRC32 Zornitza Stark Classified gene: LRRC32 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2588 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2587 LRRC32 Zornitza Stark gene: LRRC32 was added
gene: LRRC32 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Intellectual disability; cleft palate; proliferative retinopathy
Review for gene: LRRC32 was set to AMBER
Added comment: Three individuals from two consanguineous families segregated the same homozygous bi-allelic variant, c.1630C>T; p.(Arg544Ter), shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2586 NTNG2 Zornitza Stark edited their review of gene: NTNG2: Changed phenotypes: Intellectual disability, autism, dysmorphic features, Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718
Intellectual disability syndromic and non-syndromic v0.2586 NTNG2 Zornitza Stark Publications for gene: NTNG2 were set to 31668703
Intellectual disability syndromic and non-syndromic v0.2585 NTNG2 Zornitza Stark edited their review of gene: NTNG2: Added comment: Two more families reported, phenotype described as Rett-like. Both families had same homozygous frameshift mutation (chr9:135073515, c.376dupT, p.(Ser126PhefsTer241).; Changed publications: 31668703, 31692205
Intellectual disability syndromic and non-syndromic v0.2585 TAF1 Zornitza Stark Marked gene: TAF1 as ready
Intellectual disability syndromic and non-syndromic v0.2585 TAF1 Zornitza Stark Gene: taf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2585 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from to Mental retardation, X-linked, syndromic 33, MIM# 300966
Intellectual disability syndromic and non-syndromic v0.2584 TAF1 Zornitza Stark Publications for gene: TAF1 were set to
Intellectual disability syndromic and non-syndromic v0.2583 TAF1 Zornitza Stark Mode of inheritance for gene: TAF1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2582 TAF1 Zornitza Stark reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31646703; Phenotypes: Mental retardation, X-linked, syndromic 33, MIM# 300966; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2582 KCNB1 Zornitza Stark Marked gene: KCNB1 as ready
Intellectual disability syndromic and non-syndromic v0.2582 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2582 KCNB1 Zornitza Stark Phenotypes for gene: KCNB1 were changed from to Epileptic encephalopathy, early infantile, 26, MIM# 616056
Intellectual disability syndromic and non-syndromic v0.2581 KCNB1 Zornitza Stark Publications for gene: KCNB1 were set to
Intellectual disability syndromic and non-syndromic v0.2580 KCNB1 Zornitza Stark Mode of inheritance for gene: KCNB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2579 KCNB1 Zornitza Stark reviewed gene: KCNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31600826, 31513310; Phenotypes: Epileptic encephalopathy, early infantile, 26, MIM# 616056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2579 RSRC1 Zornitza Stark Classified gene: RSRC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2579 RSRC1 Zornitza Stark Gene: rsrc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2578 RSRC1 Zornitza Stark edited their review of gene: RSRC1: Added comment: 2020: 17 additional individuals reported.; Changed rating: GREEN; Changed publications: 28640246, 29522154, 32227164; Changed phenotypes: Intellectual developmental disorder, autosomal recessive 70, MIM# 618402
Intellectual disability syndromic and non-syndromic v0.2578 GAD1 Zornitza Stark Publications for gene: GAD1 were set to 15571623
Intellectual disability syndromic and non-syndromic v0.2577 GAD1 Zornitza Stark Phenotypes for gene: GAD1 were changed from Cerebral palsy, spastic quadriplegic, 1, MIM#603513 to Cerebral palsy, spastic quadriplegic, 1, MIM#603513; Developmental and epileptic encephalopathy
Intellectual disability syndromic and non-syndromic v0.2576 GAD1 Zornitza Stark Classified gene: GAD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2576 GAD1 Zornitza Stark Gene: gad1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2575 GAD1 Zornitza Stark changed review comment from: Single family reported with bi-allelic variants. Association studies linking with neuropsychiatric issues.; to: Single family reported with bi-allelic variants and CP phenotype. Association studies linking with neuropsychiatric issues.
Intellectual disability syndromic and non-syndromic v0.2575 GAD1 Zornitza Stark edited their review of gene: GAD1: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.2575 GAD1 Zornitza Stark edited their review of gene: GAD1: Added comment: 2020: 11 individuals from 6 consanguineous families reported with bi-allelic LOF variant and a developmental/epileptic encephalopathy. Seizure onset occurred in the first 2 months of life in all. All 10 individuals, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight individuals had joint contractures and/or pes equinovarus. Seven presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1−/− mouse model. Four individuals died before 4 years of age.; Changed publications: 15571623, 32282878; Changed phenotypes: Cerebral palsy, spastic quadriplegic, 1, MIM#603513, Developmental and epileptic encephalopathy
Intellectual disability syndromic and non-syndromic v0.2575 GALNT2 Zornitza Stark Marked gene: GALNT2 as ready
Intellectual disability syndromic and non-syndromic v0.2575 GALNT2 Zornitza Stark Gene: galnt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2575 GALNT2 Zornitza Stark Classified gene: GALNT2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2575 GALNT2 Zornitza Stark Gene: galnt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2574 GALNT2 Zornitza Stark gene: GALNT2 was added
gene: GALNT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALNT2 were set to 32293671
Phenotypes for gene: GALNT2 were set to Congenital disorder of glycosylation
Review for gene: GALNT2 was set to GREEN
Added comment: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2573 PLPBP Zornitza Stark Marked gene: PLPBP as ready
Intellectual disability syndromic and non-syndromic v0.2573 PLPBP Zornitza Stark Gene: plpbp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2573 PLPBP Zornitza Stark Phenotypes for gene: PLPBP were changed from to Epilepsy, early-onset, vitamin B6-dependent, MIM# 617290
Intellectual disability syndromic and non-syndromic v0.2572 PLPBP Zornitza Stark Publications for gene: PLPBP were set to
Intellectual disability syndromic and non-syndromic v0.2571 PLPBP Zornitza Stark Mode of inheritance for gene: PLPBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2570 PLPBP Zornitza Stark reviewed gene: PLPBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 27912044, 31741821, 30668673; Phenotypes: Epilepsy, early-onset, vitamin B6-dependent, MIM# 617290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2570 GRIN2A Zornitza Stark Marked gene: GRIN2A as ready
Intellectual disability syndromic and non-syndromic v0.2570 GRIN2A Zornitza Stark Gene: grin2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2570 GRIN2A Zornitza Stark Phenotypes for gene: GRIN2A were changed from to Epilepsy, focal, with speech disorder and with or without mental retardation, MIM# 245570
Intellectual disability syndromic and non-syndromic v0.2569 GRIN2A Zornitza Stark Publications for gene: GRIN2A were set to
Intellectual disability syndromic and non-syndromic v0.2568 GRIN2A Zornitza Stark Mode of pathogenicity for gene: GRIN2A was changed from to Other
Intellectual disability syndromic and non-syndromic v0.2567 GRIN2A Zornitza Stark Mode of inheritance for gene: GRIN2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2566 GRIN2A Zornitza Stark reviewed gene: GRIN2A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30544257; Phenotypes: Epilepsy, focal, with speech disorder and with or without mental retardation, MIM# 245570; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2566 TSEN34 Zornitza Stark Marked gene: TSEN34 as ready
Intellectual disability syndromic and non-syndromic v0.2566 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2566 TSEN34 Zornitza Stark Phenotypes for gene: TSEN34 were changed from to Pontocerebellar hypoplasia type 2C, MIM# 612390
Intellectual disability syndromic and non-syndromic v0.2565 TSEN34 Zornitza Stark Publications for gene: TSEN34 were set to
Intellectual disability syndromic and non-syndromic v0.2564 TSEN34 Zornitza Stark Mode of inheritance for gene: TSEN34 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2563 TSEN34 Zornitza Stark Classified gene: TSEN34 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2563 TSEN34 Zornitza Stark Gene: tsen34 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2562 TSEN34 Zornitza Stark reviewed gene: TSEN34: Rating: RED; Mode of pathogenicity: None; Publications: 18711368; Phenotypes: Pontocerebellar hypoplasia type 2C, MIM# 612390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2562 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, MIM 617159 to Sifrim-Hitz-Weiss syndrome, MIM 617159
Intellectual disability syndromic and non-syndromic v0.2561 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Intellectual disability syndromic and non-syndromic v0.2561 CHD4 Zornitza Stark Gene: chd4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2561 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, MIM 617159 to Sifrim-Hitz-Weiss syndrome, MIM 617159
Intellectual disability syndromic and non-syndromic v0.2561 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from to Sifrim-Hitz-Weiss syndrome, MIM 617159
Intellectual disability syndromic and non-syndromic v0.2561 CHD4 Zornitza Stark Publications for gene: CHD4 were set to 31388190
Intellectual disability syndromic and non-syndromic v0.2560 CHD4 Zornitza Stark Publications for gene: CHD4 were set to
Intellectual disability syndromic and non-syndromic v0.2559 CHD4 Zornitza Stark Mode of inheritance for gene: CHD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2558 CHD4 Zornitza Stark reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31388190; Phenotypes: Sifrim-Hitz-Weiss syndrome, MIM 617159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2558 TLK2 Zornitza Stark Marked gene: TLK2 as ready
Intellectual disability syndromic and non-syndromic v0.2558 TLK2 Zornitza Stark Gene: tlk2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2558 TLK2 Zornitza Stark Phenotypes for gene: TLK2 were changed from to Intellectual disability, MIM 618050; Neurodevelopmental disease
Intellectual disability syndromic and non-syndromic v0.2557 TLK2 Zornitza Stark Publications for gene: TLK2 were set to
Intellectual disability syndromic and non-syndromic v0.2556 TLK2 Zornitza Stark Mode of inheritance for gene: TLK2 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2555 TLK2 Zornitza Stark reviewed gene: TLK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29861108, 29942082, 27479843, 23911319, 30559488, 29942082, 31558842; Phenotypes: Intellectual disability, MIM 618050, Neurodevelopmental disease; 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 v0.2555 DYRK1A Zornitza Stark Marked gene: DYRK1A as ready
Intellectual disability syndromic and non-syndromic v0.2555 DYRK1A Zornitza Stark Gene: dyrk1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2555 DYRK1A Zornitza Stark Phenotypes for gene: DYRK1A were changed from to Mental retardation, autosomal dominant 7 (MIM#614104)
Intellectual disability syndromic and non-syndromic v0.2554 DYRK1A Zornitza Stark Publications for gene: DYRK1A were set to
Intellectual disability syndromic and non-syndromic v0.2553 DYRK1A Zornitza Stark Mode of inheritance for gene: DYRK1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2552 DYRK1A Zornitza Stark Deleted their review
Intellectual disability syndromic and non-syndromic v0.2552 DYRK1A Zornitza Stark reviewed gene: DYRK1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25707398, 31263215; Phenotypes: Mental retardation, autosomal dominant 7 (MIM#614104); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2552 GABRA1 Zornitza Stark Marked gene: GABRA1 as ready
Intellectual disability syndromic and non-syndromic v0.2552 GABRA1 Zornitza Stark Gene: gabra1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2552 GABRA1 Zornitza Stark Phenotypes for gene: GABRA1 were changed from to Epileptic encephalopathy, early infantile, 19 615744; Rett syndrome; Rett-like phenotypes; idiopathic generalized Epilepsy; Dravet syndrome
Intellectual disability syndromic and non-syndromic v0.2551 GABRA1 Zornitza Stark Publications for gene: GABRA1 were set to
Intellectual disability syndromic and non-syndromic v0.2550 GABRA1 Zornitza Stark Mode of inheritance for gene: GABRA1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2549 GABRA1 Zornitza Stark reviewed gene: GABRA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11992121, 21714819, 24623842, 30842224; Phenotypes: Epileptic encephalopathy, early infantile, 19 615744, Rett syndrome, Rett-like phenotypes, idiopathic generalized Epilepsy, Dravet syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2549 GNAI2 Zornitza Stark Marked gene: GNAI2 as ready
Intellectual disability syndromic and non-syndromic v0.2549 GNAI2 Zornitza Stark Gene: gnai2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2549 GNAI2 Zornitza Stark Classified gene: GNAI2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2549 GNAI2 Zornitza Stark Gene: gnai2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2548 GNAI2 Zornitza Stark changed review comment from: Single individual with de novo variant reported.
Sources: Literature; to: Two individuals reported, some functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2548 GNAI2 Zornitza Stark edited their review of gene: GNAI2: Changed rating: AMBER; Changed publications: 31036916, 27787898
Intellectual disability syndromic and non-syndromic v0.2548 GNAI2 Zornitza Stark gene: GNAI2 was added
gene: GNAI2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GNAI2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAI2 were set to 31036916
Phenotypes for gene: GNAI2 were set to Syndromic intellectual disability
Review for gene: GNAI2 was set to RED
Added comment: Single individual with de novo variant reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2547 FEM1B Zornitza Stark Marked gene: FEM1B as ready
Intellectual disability syndromic and non-syndromic v0.2547 FEM1B Zornitza Stark Gene: fem1b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2547 FEM1B Zornitza Stark Classified gene: FEM1B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2547 FEM1B Zornitza Stark Gene: fem1b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2546 FEM1B Zornitza Stark gene: FEM1B was added
gene: FEM1B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FEM1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEM1B were set to 31036916
Phenotypes for gene: FEM1B were set to Syndromic intellectual disability
Review for gene: FEM1B was set to AMBER
Added comment: No OMIM phenotype PMID: 31036916 - a single de novo patient reported in a neurodevelopmental disorder cohort. Authors note another de novo case with the exact same variant (p.Arg126Gln) from the DDD study, and a 3rd patient from GeneMatcher with the same de novo missense again. Decipher shows this variant to be in a highly constrained region of the protein. Cannot be certain the DDD and GeneMatcher individuals are unrelated, therefore treat as two reports for now.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2545 WIPI2 Zornitza Stark Marked gene: WIPI2 as ready
Intellectual disability syndromic and non-syndromic v0.2545 WIPI2 Zornitza Stark Gene: wipi2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2545 SLC44A1 Zornitza Stark Marked gene: SLC44A1 as ready
Intellectual disability syndromic and non-syndromic v0.2545 SLC44A1 Zornitza Stark Added comment: Comment when marking as ready: Progressive neurodegenerative disorder rather than true intellectual disability. The first characteristic neurological abnormalities were noted between the ages of 2–8 years. Cardinal features included tremor, dysarthria, swallowing difficulties, ataxia, truncal muscle weakness, strabismus, and decreased visual acuity.
Intellectual disability syndromic and non-syndromic v0.2545 SLC44A1 Zornitza Stark Gene: slc44a1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2545 WIPI2 Zornitza Stark gene: WIPI2 was added
gene: WIPI2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WIPI2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WIPI2 were set to 30968111
Phenotypes for gene: WIPI2 were set to Intellectual developmental disorder with short stature and variable skeletal anomalies 618453
Review for gene: WIPI2 was set to RED
Added comment: Four homozygous individuals from one consanguineous family with intellectual disability, short stature and variable skeletal anomalies. Functional studies in patient cells showed impaired protein function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2544 MAB21L1 Kristin Rigbye edited their review of gene: MAB21L1: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.2544 GSX2 Zornitza Stark Marked gene: GSX2 as ready
Intellectual disability syndromic and non-syndromic v0.2544 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2544 GSX2 Zornitza Stark Classified gene: GSX2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2544 GSX2 Zornitza Stark Gene: gsx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2543 GSX2 Zornitza Stark gene: GSX2 was added
gene: GSX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GSX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSX2 were set to 31412107
Phenotypes for gene: GSX2 were set to Diencephalic-mesencephalic junction dysplasia syndrome 2 618646; Intellectual disability; Dystonia; Spastic tetra paresis
Review for gene: GSX2 was set to AMBER
Added comment: Two unrelated families, some functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2542 IGF1R Zornitza Stark Marked gene: IGF1R as ready
Intellectual disability syndromic and non-syndromic v0.2542 IGF1R Zornitza Stark Gene: igf1r has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2542 IGF1R Zornitza Stark Phenotypes for gene: IGF1R were changed from to Insulin-like growth factor I, resistance to, MIM# 270450
Intellectual disability syndromic and non-syndromic v0.2541 IGF1R Zornitza Stark Publications for gene: IGF1R were set to 31586944
Intellectual disability syndromic and non-syndromic v0.2541 IGF1R Zornitza Stark Publications for gene: IGF1R were set to
Intellectual disability syndromic and non-syndromic v0.2540 YARS Zornitza Stark Marked gene: YARS as ready
Intellectual disability syndromic and non-syndromic v0.2540 YARS Zornitza Stark Gene: yars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2540 YARS Zornitza Stark Classified gene: YARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2540 YARS Zornitza Stark Gene: yars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2539 YARS Zornitza Stark gene: YARS was added
gene: YARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: YARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YARS were set to 30304524; 29232904; 27633801
Phenotypes for gene: YARS were set to Intellectual disability; deafness; nystagmus; liver dysfunction
Review for gene: YARS was set to GREEN
Added comment: Mono-allelic variants are associated with CMT. However, 10 individuals from three unrelated families reported with bi-allelic variants and a severe phenotype, comprising ID, nystagmus, deafness, liver dysfunction and a range of other features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2538 DYRK1A Crystle Lee reviewed gene: DYRK1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25707398; Phenotypes: Mental retardation, autosomal dominant 7 (MIM#614104); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2538 IGF1R Zornitza Stark Mode of inheritance for gene: IGF1R was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2537 IGF1R Zornitza Stark Mode of inheritance for gene: IGF1R was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2536 IGF1R Zornitza Stark reviewed gene: IGF1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 31586944; Phenotypes: Insulin-like growth factor I, resistance to, MIM# 270450; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2536 SLC44A1 Sebastian Lunke gene: SLC44A1 was added
gene: SLC44A1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC44A1 were set to 31855247
Phenotypes for gene: SLC44A1 were set to progressive ataxia; tremor; cognitive decline; dysphagia; optic atrophy; dysarthria
Review for gene: SLC44A1 was set to GREEN
gene: SLC44A1 was marked as current diagnostic
Added comment: Four affected individuals from three families with homozygous frameshift variants. Functional evidence points to impaired choline transporter function yet unchanged membrane phosphatidylcholine content. Choline treatments may be beneficial.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2535 CTCF Zornitza Stark Marked gene: CTCF as ready
Intellectual disability syndromic and non-syndromic v0.2535 CTCF Zornitza Stark Gene: ctcf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2535 CTCF Zornitza Stark Phenotypes for gene: CTCF were changed from to Mental retardation, autosomal dominant 21 (MIM#615502)
Intellectual disability syndromic and non-syndromic v0.2534 CTCF Zornitza Stark Publications for gene: CTCF were set to
Intellectual disability syndromic and non-syndromic v0.2533 CTCF Zornitza Stark Mode of inheritance for gene: CTCF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2532 CTCF Crystle Lee reviewed gene: CTCF: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746550, 31239556; Phenotypes: Mental retardation, autosomal dominant 21 (MIM#615502); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.2532 MAB21L1 Zornitza Stark Publications for gene: MAB21L1 were set to 30487245
Intellectual disability syndromic and non-syndromic v0.2531 ZMYND11 Zornitza Stark Marked gene: ZMYND11 as ready
Intellectual disability syndromic and non-syndromic v0.2531 ZMYND11 Zornitza Stark Gene: zmynd11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2531 ZMYND11 Zornitza Stark Phenotypes for gene: ZMYND11 were changed from to Mental retardation, autosomal dominant 30, MIM# 616083
Intellectual disability syndromic and non-syndromic v0.2530 ZMYND11 Zornitza Stark Publications for gene: ZMYND11 were set to
Intellectual disability syndromic and non-syndromic v0.2529 ZMYND11 Zornitza Stark Mode of inheritance for gene: ZMYND11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2528 ZMYND11 Zornitza Stark reviewed gene: ZMYND11: Rating: GREEN; Mode of pathogenicity: None; Publications: 32097528; Phenotypes: Mental retardation, autosomal dominant 30, MIM# 616083; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2528 MAB21L1 Kristin Rigbye reviewed gene: MAB21L1: Rating: ; Mode of pathogenicity: None; Publications: 27103078, 30487245; Phenotypes: Syndromic scrotal agenesis, syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome), Cerebello-Oculo-Facio-Genital syndrome; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2528 BAZ2B Zornitza Stark Marked gene: BAZ2B as ready
Intellectual disability syndromic and non-syndromic v0.2528 BAZ2B Zornitza Stark Gene: baz2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2528 BAZ2B Zornitza Stark Classified gene: BAZ2B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2528 BAZ2B Zornitza Stark Gene: baz2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2527 BAZ2B Zornitza Stark gene: BAZ2B was added
gene: BAZ2B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BAZ2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAZ2B were set to 31999386
Phenotypes for gene: BAZ2B were set to Intellectual disability; autism
Review for gene: BAZ2B was set to GREEN
Added comment: Postulated as a candidate gene for ID/ASD by large-scale studies. Case series reports two individuals with small CNVs and and six with SNVs, mostly LoF type variants. Although the gene is generally intolerant of LoF, some LoF variants present in gnomad ?incomplete penetrance. Additional reported features were inconsistent
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2526 CACNB4 Bryony Thompson Classified gene: CACNB4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2526 CACNB4 Bryony Thompson Gene: cacnb4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2525 CACNB4 Bryony Thompson gene: CACNB4 was added
gene: CACNB4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CACNB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNB4 were set to 32176688
Phenotypes for gene: CACNB4 were set to intellectual disability; psychomotor retardation; blindness; epilepsy; movement disorder; cerebellar atrophy
Review for gene: CACNB4 was set to AMBER
Added comment: A homozygous missense variant (Leu126Pro) was identified in two siblings with intellectual disability, psychomotor retardation, blindness, epilepsy, movement disorder and cerebellar atrophy. In vitro functional assays of the variant identify three potential pathomechanisms: impairs the formation of synaptic P/Q-type calcium channel complexes; prevents activity-dependent nuclear targeting and thus β4-dependent nuclear functions; disturbs complex formation between β4b and the TRAF2 and NCK interacting kinase TNIK.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2524 FMR1 Bryony Thompson Tag STR tag was added to gene: FMR1.
Intellectual disability syndromic and non-syndromic v0.2524 SLC18A2 Zornitza Stark Marked gene: SLC18A2 as ready
Intellectual disability syndromic and non-syndromic v0.2524 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2524 SLC18A2 Zornitza Stark Classified gene: SLC18A2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2524 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2523 SLC18A2 Zornitza Stark gene: SLC18A2 was added
gene: SLC18A2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A2 were set to 23363473; 31240161; 26497564
Phenotypes for gene: SLC18A2 were set to Parkinsonism-dystonia, infantile, 2, MIM# 618049
Review for gene: SLC18A2 was set to GREEN
Added comment: At least three unrelated families reported, potential treatment implications.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2522 KMT2E Zornitza Stark reviewed gene: KMT2E: Rating: GREEN; Mode of pathogenicity: None; Publications: 31079897; Phenotypes: O'Donnell-Luria-Rodan syndrome, MIM# 618512, Intellectual disability, Autism, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2522 NRROS Zornitza Stark Marked gene: NRROS as ready
Intellectual disability syndromic and non-syndromic v0.2522 NRROS Zornitza Stark Gene: nrros has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2522 RUBCN Zornitza Stark Mode of inheritance for gene: RUBCN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2521 RUBCN Zornitza Stark edited their review of gene: RUBCN: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2521 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract to microcephaly; ID; cataract; structural brain abnormalities; hypoventilation
Intellectual disability syndromic and non-syndromic v0.2520 NUP188 Zornitza Stark Publications for gene: NUP188 were set to https://doi.org/10.1159/000504818; 28726809
Intellectual disability syndromic and non-syndromic v0.2519 NUP188 Zornitza Stark Classified gene: NUP188 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2519 NUP188 Zornitza Stark Gene: nup188 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2518 NUP188 Zornitza Stark changed review comment from: Additional 6 unrelated individuals reported, promoted to Green.; to: Additional 6 unrelated individuals with bi-allelic LoF variants reported, promoted to Green.
Intellectual disability syndromic and non-syndromic v0.2518 NUP188 Zornitza Stark edited their review of gene: NUP188: Added comment: Additional 6 unrelated individuals reported, promoted to Green.; Changed rating: GREEN; Changed publications: 32021605, 28726809, 32275884; Changed phenotypes: microcephaly, ID, cataract, structural brain abnormalities, hypoventilation
Intellectual disability syndromic and non-syndromic v0.2518 NDUFS4 Zornitza Stark reviewed gene: NDUFS4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10944442, 27079373, 19107570, 12616398; Phenotypes: Mitochondrial complex I deficiency, nuclear type 1, 252010, Leigh syndrome, MIM#252010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2518 AP3B2 Zornitza Stark Marked gene: AP3B2 as ready
Intellectual disability syndromic and non-syndromic v0.2518 AP3B2 Zornitza Stark Gene: ap3b2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2518 AP3B2 Zornitza Stark Phenotypes for gene: AP3B2 were changed from to Early-onset epileptic encephalopathy with optic atrophy, MIM#617276
Intellectual disability syndromic and non-syndromic v0.2517 AP3B2 Zornitza Stark Publications for gene: AP3B2 were set to
Intellectual disability syndromic and non-syndromic v0.2516 AP3B2 Zornitza Stark Mode of inheritance for gene: AP3B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2515 AP3B2 Zornitza Stark reviewed gene: AP3B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27889060; Phenotypes: Early-onset epileptic encephalopathy with optic atrophy, MIM#617276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2515 TCF20 Zornitza Stark Marked gene: TCF20 as ready
Intellectual disability syndromic and non-syndromic v0.2515 TCF20 Zornitza Stark Gene: tcf20 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2515 TCF20 Zornitza Stark Phenotypes for gene: TCF20 were changed from to Developmental delay with variable intellectual impairment and behavioral abnormalities, AD, MIM#618430
Intellectual disability syndromic and non-syndromic v0.2514 TCF20 Zornitza Stark Publications for gene: TCF20 were set to
Intellectual disability syndromic and non-syndromic v0.2513 TCF20 Zornitza Stark Mode of inheritance for gene: TCF20 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2512 TCF20 Zornitza Stark reviewed gene: TCF20: Rating: GREEN; Mode of pathogenicity: None; Publications: 30739909, 30819258, 25228304; Phenotypes: Developmental delay with variable intellectual impairment and behavioral abnormalities, AD, MIM#618430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2512 TFE3 Zornitza Stark Marked gene: TFE3 as ready
Intellectual disability syndromic and non-syndromic v0.2512 TFE3 Zornitza Stark Gene: tfe3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2512 TFE3 Zornitza Stark Classified gene: TFE3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2512 TFE3 Zornitza Stark Gene: tfe3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2511 TFE3 Zornitza Stark gene: TFE3 was added
gene: TFE3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TFE3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TFE3 were set to 30595499; 31833172
Phenotypes for gene: TFE3 were set to TFE3-associated neurodevelopmental disorder; Intellectual disability; Epilepsy; Coarse facial features
Review for gene: TFE3 was set to GREEN
Added comment: Seven individuals reported; so far, all have been found to harbour de novo variants affecting exons 3 or 4.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2510 TOP2B Zornitza Stark Marked gene: TOP2B as ready
Intellectual disability syndromic and non-syndromic v0.2510 TOP2B Zornitza Stark Gene: top2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2510 TOP2B Zornitza Stark Classified gene: TOP2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2510 TOP2B Zornitza Stark Gene: top2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2509 TOP2B Zornitza Stark gene: TOP2B was added
gene: TOP2B was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOP2B were set to 31953910; 28343847; 12773624
Phenotypes for gene: TOP2B were set to Intellectual disability
Review for gene: TOP2B was set to AMBER
Added comment: Two unrelated individuals reported with the same de novo variant, c.187C > T, p.(His63Tyr) and also mouse model data supports role in brain development. Gene has also been associated independently with deafness and with immunodeficiency and the variant-disease relationship remains to be fully elucidated.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2508 CNKSR1 Zornitza Stark Marked gene: CNKSR1 as ready
Intellectual disability syndromic and non-syndromic v0.2508 CNKSR1 Zornitza Stark Gene: cnksr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2508 CNKSR1 Zornitza Stark Classified gene: CNKSR1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2508 CNKSR1 Zornitza Stark Gene: cnksr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2507 CNKSR1 Zornitza Stark gene: CNKSR1 was added
gene: CNKSR1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: CNKSR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CNKSR1 were set to 30450701; 30237576; 21937992
Phenotypes for gene: CNKSR1 were set to Intellectual disability
Review for gene: CNKSR1 was set to AMBER
Added comment: Three families reported, two as part of large cohorts reporting multiple novel genes. Note the family reported in PMID 30450701 appears to be the same family as reported in PMID 21937992. Some functional data in PMID 30450701, including Drosophila model.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2506 FRMD4A Zornitza Stark Marked gene: FRMD4A as ready
Intellectual disability syndromic and non-syndromic v0.2506 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2506 FRMD4A Zornitza Stark Phenotypes for gene: FRMD4A were changed from Intellectual disability; microcephaly to Intellectual disability; microcephaly; Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, MIM# 616819
Intellectual disability syndromic and non-syndromic v0.2505 FRMD4A Zornitza Stark Classified gene: FRMD4A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2505 FRMD4A Zornitza Stark Gene: frmd4a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2504 FRMD4A Zornitza Stark edited their review of gene: FRMD4A: Changed phenotypes: Intellectual disability, microcephaly, Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, MIM# 616819
Intellectual disability syndromic and non-syndromic v0.2504 FRMD4A Zornitza Stark edited their review of gene: FRMD4A: Changed phenotypes: Intellectual disability, microcephaly, Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia 616819
Intellectual disability syndromic and non-syndromic v0.2504 FRMD4A Zornitza Stark gene: FRMD4A was added
gene: FRMD4A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: FRMD4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRMD4A were set to 25388005; 30214071
Phenotypes for gene: FRMD4A were set to Intellectual disability; microcephaly
Review for gene: FRMD4A was set to AMBER
Added comment: Single Bedouin Israeli family reported with homozygous variant initially. Good segregation data. No functional data. Another family reported as part of a large consanguineous microcephaly cohort, different variant.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2503 PIGK Zornitza Stark Classified gene: PIGK as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2503 PIGK Zornitza Stark Gene: pigk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2502 PIGK Zornitza Stark gene: PIGK was added
gene: PIGK was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PIGK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGK were set to 32220290
Phenotypes for gene: PIGK were set to Intellectual disability; seizures; cerebellar atrophy
Review for gene: PIGK was set to GREEN
Added comment: 12 individuals from 9 unrelated families reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2501 ADARB1 Zornitza Stark Marked gene: ADARB1 as ready
Intellectual disability syndromic and non-syndromic v0.2501 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2501 ADARB1 Zornitza Stark Classified gene: ADARB1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2501 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2500 ADARB1 Zornitza Stark Classified gene: ADARB1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2500 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2500 ADARB1 Zornitza Stark Classified gene: ADARB1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2500 ADARB1 Zornitza Stark Gene: adarb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2499 ADARB1 Zornitza Stark gene: ADARB1 was added
gene: ADARB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ADARB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADARB1 were set to 32220291
Phenotypes for gene: ADARB1 were set to Intellectual disability; microcephaly; seizures
Review for gene: ADARB1 was set to GREEN
Added comment: Four unrelated individuals with bi-allelic variants in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2498 PQBP1 Zornitza Stark Marked gene: PQBP1 as ready
Intellectual disability syndromic and non-syndromic v0.2498 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2498 PQBP1 Zornitza Stark Phenotypes for gene: PQBP1 were changed from to Renpenning syndrome, MIM#309500
Intellectual disability syndromic and non-syndromic v0.2497 PQBP1 Zornitza Stark Publications for gene: PQBP1 were set to
Intellectual disability syndromic and non-syndromic v0.2496 PQBP1 Zornitza Stark Mode of inheritance for gene: PQBP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2495 PQBP1 Zornitza Stark reviewed gene: PQBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31840929, 14634649, 20410308; Phenotypes: Renpenning syndrome, MIM#309500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2495 DLG3 Zornitza Stark Marked gene: DLG3 as ready
Intellectual disability syndromic and non-syndromic v0.2495 DLG3 Zornitza Stark Gene: dlg3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2495 DLG3 Zornitza Stark Phenotypes for gene: DLG3 were changed from to Mental retardation, X-linked 90, MIM#300850
Intellectual disability syndromic and non-syndromic v0.2494 DLG3 Zornitza Stark Publications for gene: DLG3 were set to
Intellectual disability syndromic and non-syndromic v0.2493 DLG3 Zornitza Stark Mode of inheritance for gene: DLG3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2492 DLG3 Zornitza Stark reviewed gene: DLG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28777483, 24721225; Phenotypes: Mental retardation, X-linked 90, MIM#300850; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2492 AGTPBP1 Zornitza Stark Marked gene: AGTPBP1 as ready
Intellectual disability syndromic and non-syndromic v0.2492 AGTPBP1 Zornitza Stark Gene: agtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2492 AGTPBP1 Zornitza Stark Classified gene: AGTPBP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2492 AGTPBP1 Zornitza Stark Gene: agtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2491 AGTPBP1 Zornitza Stark gene: AGTPBP1 was added
gene: AGTPBP1 was added to Intellectual disability syndromic and non-syndromic. Sources: NHS GMS
Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGTPBP1 were set to 30420557
Phenotypes for gene: AGTPBP1 were set to Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276
Review for gene: AGTPBP1 was set to GREEN
Added comment: Thirteen individuals reported, clinical presentation was with developmental delay, though six went on to have a progressive neurological course. Other features include cerebellar atrophy and neuropathy.
Sources: NHS GMS
Intellectual disability syndromic and non-syndromic v0.2490 ADGRG6 Zornitza Stark reviewed gene: ADGRG6: Rating: RED; Mode of pathogenicity: None; Publications: 30549416, 26004201; Phenotypes: Lethal congenital contracture syndrome 9, OMIM #616503; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2490 NAA15 Ee Ming Wong reviewed gene: NAA15: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31127942; Phenotypes: Mental retardation, autosomal dominant 50, 617787 (3), NAA15-related syndrome (PMID: 31127942); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.2490 NR2F2 Sue White Classified gene: NR2F2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2490 NR2F2 Sue White Gene: nr2f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2489 NR2F2 Sue White gene: NR2F2 was added
gene: NR2F2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NR2F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F2 were set to 29478779; 29663647
Phenotypes for gene: NR2F2 were set to mild intellectual disability; congenital heart disease; disorder of sexual differentiation; dysmorphic features
Penetrance for gene: NR2F2 were set to Complete
Review for gene: NR2F2 was set to AMBER
Added comment: Established gene for congenital heart disease and DSD and emerging gene for ID. 2 unrelated individuals published with mild or borderline ID, dysmorphism and de novo truncating/missense variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2488 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2488 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2487 EIF2AK2 Zornitza Stark gene: EIF2AK2 was added
gene: EIF2AK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to 32197074
Phenotypes for gene: EIF2AK2 were set to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness
Review for gene: EIF2AK2 was set to GREEN
Added comment: Eight individuals with de novo variants and complex neurodevelopmental phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2486 EIF2AK1 Zornitza Stark Marked gene: EIF2AK1 as ready
Intellectual disability syndromic and non-syndromic v0.2486 EIF2AK1 Zornitza Stark Gene: eif2ak1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2486 EIF2AK1 Zornitza Stark gene: EIF2AK1 was added
gene: EIF2AK1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EIF2AK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK1 were set to 32197074
Phenotypes for gene: EIF2AK1 were set to Intellectual disability; white matter abnormalities
Review for gene: EIF2AK1 was set to RED
Added comment: Single individual reported with de novo variant in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2485 NOVA2 Zornitza Stark Marked gene: NOVA2 as ready
Intellectual disability syndromic and non-syndromic v0.2485 NOVA2 Zornitza Stark Gene: nova2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2485 NOVA2 Zornitza Stark Classified gene: NOVA2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2485 NOVA2 Zornitza Stark Gene: nova2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2484 NOVA2 Zornitza Stark gene: NOVA2 was added
gene: NOVA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOVA2 were set to 32197073
Phenotypes for gene: NOVA2 were set to Intellectual disability; autism; hypotonia; spasticity; ataxia
Mode of pathogenicity for gene: NOVA2 was set to Other
Review for gene: NOVA2 was set to GREEN
Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2483 GNB2 Sue White Classified gene: GNB2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2483 GNB2 Sue White Gene: gnb2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2482 GNB2 Sue White gene: GNB2 was added
gene: GNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB2 were set to 31698099
Phenotypes for gene: GNB2 were set to intellectual disability; dysmorphic features
Review for gene: GNB2 was set to AMBER
Added comment: emerging evidence of de novo missense variants in patients with intellectual disability
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2481 NRROS Sue White Classified gene: NRROS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2481 NRROS Sue White Gene: nrros has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2480 NRROS Sue White gene: NRROS was added
gene: NRROS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NRROS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRROS were set to 32197075; 32100099
Phenotypes for gene: NRROS were set to neurodegeneration; intracranial calcification; epilepsy
Penetrance for gene: NRROS were set to Complete
Review for gene: NRROS was set to GREEN
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2479 CNOT3 Zornitza Stark Marked gene: CNOT3 as ready
Intellectual disability syndromic and non-syndromic v0.2479 CNOT3 Zornitza Stark Added comment: Comment when marking as ready: 16 unrelated individuals reported.
Intellectual disability syndromic and non-syndromic v0.2479 CNOT3 Zornitza Stark Gene: cnot3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2479 CNOT3 Zornitza Stark Marked gene: CNOT3 as ready
Intellectual disability syndromic and non-syndromic v0.2479 CNOT3 Zornitza Stark Gene: cnot3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2479 CNOT3 Zornitza Stark Phenotypes for gene: CNOT3 were changed from to Intellectual developmental disorder with speech delay, autism, and dysmorphic facies 618672
Intellectual disability syndromic and non-syndromic v0.2478 CNOT3 Zornitza Stark Publications for gene: CNOT3 were set to
Intellectual disability syndromic and non-syndromic v0.2477 CNOT3 Zornitza Stark Mode of inheritance for gene: CNOT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2476 CNOT3 Teresa Zhao reviewed gene: CNOT3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31201375; Phenotypes: Intellectual developmental disorder with speech delay, autism, and dysmorphic facies 618672; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2476 QARS Zornitza Stark Marked gene: QARS as ready
Intellectual disability syndromic and non-syndromic v0.2476 QARS Zornitza Stark Gene: qars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2476 QARS Zornitza Stark Phenotypes for gene: QARS were changed from to Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, MIM# 615760
Intellectual disability syndromic and non-syndromic v0.2475 QARS Zornitza Stark Publications for gene: QARS were set to
Intellectual disability syndromic and non-syndromic v0.2474 QARS Zornitza Stark Mode of inheritance for gene: QARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2473 QARS Zornitza Stark reviewed gene: QARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 28620870, 25471517, 25432320, 25041233, 24656866, 32042906; Phenotypes: Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, MIM# 615760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2473 MRPL3 Zornitza Stark reviewed gene: MRPL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27815843, 21786366; Phenotypes: Combined oxidative phosphorylation deficiency 9, OMIM #614582; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2473 SPATA5 Zornitza Stark Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome MIM#616577 to Epilepsy, hearing loss, and mental retardation syndrome MIM#616577
Intellectual disability syndromic and non-syndromic v0.2473 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Intellectual disability syndromic and non-syndromic v0.2473 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2473 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Intellectual disability syndromic and non-syndromic v0.2473 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2473 SPATA5 Zornitza Stark Phenotypes for gene: SPATA5 were changed from to Epilepsy, hearing loss, and mental retardation syndrome MIM#616577
Intellectual disability syndromic and non-syndromic v0.2472 SPATA5 Zornitza Stark Publications for gene: SPATA5 were set to
Intellectual disability syndromic and non-syndromic v0.2471 SPATA5 Zornitza Stark Mode of inheritance for gene: SPATA5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2470 SPATA5 Zornitza Stark reviewed gene: SPATA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30009132, 29343804; Phenotypes: Epilepsy, hearing loss, and mental retardation syndrome MIM#616577; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2470 ISCA1 Zornitza Stark Marked gene: ISCA1 as ready
Intellectual disability syndromic and non-syndromic v0.2470 ISCA1 Zornitza Stark Gene: isca1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2470 ISCA1 Zornitza Stark Classified gene: ISCA1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2470 ISCA1 Zornitza Stark Gene: isca1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2469 ISCA1 Zornitza Stark gene: ISCA1 was added
gene: ISCA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: ISCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISCA1 were set to 28356563; 32092383; 31016283; 30113620; 30105122
Phenotypes for gene: ISCA1 were set to Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613
Review for gene: ISCA1 was set to GREEN
gene: ISCA1 was marked as current diagnostic
Added comment: Multiple unrelated families reported. Severe disorder characterised by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Rat model results in early lethality. Founder variant c.259G > A, p.(Glu87Lys) reported in Indian families.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2468 CAMTA1 Zornitza Stark Publications for gene: CAMTA1 were set to
Intellectual disability syndromic and non-syndromic v0.2467 CAMTA1 Zornitza Stark Tag SV/CNV tag was added to gene: CAMTA1.
Intellectual disability syndromic and non-syndromic v0.2467 CAMTA1 Zornitza Stark reviewed gene: CAMTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32157189, 22693284; Phenotypes: Cerebellar ataxia, nonprogressive, with mental retardation (614756 AD); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2467 GPT2 Zornitza Stark Marked gene: GPT2 as ready
Intellectual disability syndromic and non-syndromic v0.2467 GPT2 Zornitza Stark Gene: gpt2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2467 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from to Mental retardation, autosomal recessive 49, MIM#616281
Intellectual disability syndromic and non-syndromic v0.2466 GPT2 Zornitza Stark Publications for gene: GPT2 were set to
Intellectual disability syndromic and non-syndromic v0.2465 GPT2 Zornitza Stark Mode of inheritance for gene: GPT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2464 GPT2 Chern Lim reviewed gene: GPT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27601654, 25758935; Phenotypes: Mental retardation, autosomal recessive 49, MIM#616281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2463 SUPT16H Zornitza Stark Marked gene: SUPT16H as ready
Intellectual disability syndromic and non-syndromic v0.2463 SUPT16H Zornitza Stark Gene: supt16h has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2463 SUPT16H Zornitza Stark Classified gene: SUPT16H as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2463 SUPT16H Zornitza Stark Gene: supt16h has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2462 SUPT16H Zornitza Stark gene: SUPT16H was added
gene: SUPT16H was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SUPT16H was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUPT16H were set to 31924697
Phenotypes for gene: SUPT16H were set to Intellectual disability; Abnormality of the corpus callosum
Review for gene: SUPT16H was set to GREEN
Added comment: Four unrelated individuals with de novo missense variants in this gene. Publication also reports on a deletion, but note this includes other genes and the individual also had another CNV.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2461 SLC5A6 Zornitza Stark Publications for gene: SLC5A6 were set to 31754459; 27904971
Intellectual disability syndromic and non-syndromic v0.2460 SLC5A6 Zornitza Stark changed review comment from: Two unrelated families reported, functional data and some evidence of response to treatment.
Sources: Literature; to: Three unrelated families reported, functional data and some evidence of response to treatment.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2460 SLC5A6 Zornitza Stark edited their review of gene: SLC5A6: Changed publications: 31754459, 27904971, 31392107
Intellectual disability syndromic and non-syndromic v0.2460 RARS Zornitza Stark Marked gene: RARS as ready
Intellectual disability syndromic and non-syndromic v0.2460 RARS Zornitza Stark Gene: rars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2460 RARS Zornitza Stark Classified gene: RARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2460 RARS Zornitza Stark Gene: rars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2459 RARS Zornitza Stark gene: RARS was added
gene: RARS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: RARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RARS were set to 31814314
Phenotypes for gene: RARS were set to Leukodystrophy, hypomyelinating, 9 MIM# 616140
Review for gene: RARS was set to GREEN
gene: RARS was marked as current diagnostic
Added comment: 15 families reported, DD/ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2458 CXorf56 Zornitza Stark Classified gene: CXorf56 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2458 CXorf56 Zornitza Stark Gene: cxorf56 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2457 CXorf56 Zornitza Stark edited their review of gene: CXorf56: Added comment: Additional report of three more families, upgrade to Green.; Changed rating: GREEN; Changed publications: 29374277, 31822863; Changed phenotypes: Mental retardation, X-linked 107, MIM# 301013
Intellectual disability syndromic and non-syndromic v0.2457 TNR Zornitza Stark Marked gene: TNR as ready
Intellectual disability syndromic and non-syndromic v0.2457 TNR Zornitza Stark Gene: tnr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2457 TNR Zornitza Stark Classified gene: TNR as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2457 TNR Zornitza Stark Gene: tnr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2456 TNR Zornitza Stark gene: TNR was added
gene: TNR was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TNR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNR were set to 32099069
Phenotypes for gene: TNR were set to Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus
Review for gene: TNR was set to GREEN
Added comment: 13 individuals from 8 unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2455 RSPRY1 Zornitza Stark changed review comment from: Two unrelated individuals reported, some functional evidence.
Sources: Expert list; to: Two unrelated individuals reported, some functional evidence. Dev delay/autism part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2455 RSPRY1 Zornitza Stark Classified gene: RSPRY1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2455 RSPRY1 Zornitza Stark Gene: rspry1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2454 RSPRY1 Zornitza Stark gene: RSPRY1 was added
gene: RSPRY1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: RSPRY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSPRY1 were set to 26365341
Phenotypes for gene: RSPRY1 were set to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585
Review for gene: RSPRY1 was set to AMBER
Added comment: Two unrelated individuals reported, some functional evidence.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2453 RPS23 Zornitza Stark Phenotypes for gene: RPS23 were changed from Brachycephaly, trichomegaly, and developmental delay, MIM# 617412 to Brachycephaly, trichomegaly, and developmental delay, MIM# 617412
Intellectual disability syndromic and non-syndromic v0.2453 RPS23 Zornitza Stark Marked gene: RPS23 as ready
Intellectual disability syndromic and non-syndromic v0.2453 RPS23 Zornitza Stark Gene: rps23 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2453 RPS23 Zornitza Stark Phenotypes for gene: RPS23 were changed from to Brachycephaly, trichomegaly, and developmental delay, MIM# 617412
Intellectual disability syndromic and non-syndromic v0.2452 RPS23 Zornitza Stark Publications for gene: RPS23 were set to 28257692
Intellectual disability syndromic and non-syndromic v0.2452 RPS23 Zornitza Stark Publications for gene: RPS23 were set to
Intellectual disability syndromic and non-syndromic v0.2451 RPS23 Zornitza Stark Mode of inheritance for gene: RPS23 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2450 RPS23 Zornitza Stark Classified gene: RPS23 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2450 RPS23 Zornitza Stark Gene: rps23 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2449 RPS23 Zornitza Stark reviewed gene: RPS23: Rating: AMBER; Mode of pathogenicity: None; Publications: 28257692; Phenotypes: Brachycephaly, trichomegaly, and developmental delay, MIM# 617412; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2449 RNF13 Zornitza Stark Marked gene: RNF13 as ready
Intellectual disability syndromic and non-syndromic v0.2449 RNF13 Zornitza Stark Gene: rnf13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2449 RNF13 Zornitza Stark Classified gene: RNF13 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2449 RNF13 Zornitza Stark Gene: rnf13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2448 RNF13 Zornitza Stark gene: RNF13 was added
gene: RNF13 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: RNF13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNF13 were set to 30595371
Phenotypes for gene: RNF13 were set to Epileptic encephalopathy, early infantile, 73 618379
Mode of pathogenicity for gene: RNF13 was set to Other
Review for gene: RNF13 was set to GREEN
Added comment: Three unrelated individuals with de novo variants in this gene and severe neurological phenotype, including microcephaly, seizures, visual impairment, profound developmental delay.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2447 RIMS1 Zornitza Stark Marked gene: RIMS1 as ready
Intellectual disability syndromic and non-syndromic v0.2447 RIMS1 Zornitza Stark Gene: rims1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2447 RIMS1 Zornitza Stark Phenotypes for gene: RIMS1 were changed from to Autism; Cone-rod dystrophy 7 , MIM#603649
Intellectual disability syndromic and non-syndromic v0.2446 RIMS1 Zornitza Stark Publications for gene: RIMS1 were set to
Intellectual disability syndromic and non-syndromic v0.2445 RIMS1 Zornitza Stark Mode of inheritance for gene: RIMS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2444 RIMS1 Zornitza Stark Classified gene: RIMS1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2444 RIMS1 Zornitza Stark Gene: rims1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2443 RIMS1 Zornitza Stark reviewed gene: RIMS1: Rating: RED; Mode of pathogenicity: None; Publications: 25284784, 12659814; Phenotypes: Autism, Cone-rod dystrophy 7 , MIM#603649; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2443 RHEB Zornitza Stark Marked gene: RHEB as ready
Intellectual disability syndromic and non-syndromic v0.2443 RHEB Zornitza Stark Gene: rheb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2443 RHEB Zornitza Stark Phenotypes for gene: RHEB were changed from to Intellectual disability; Macrocephaly; Focal cortical dysplasia
Intellectual disability syndromic and non-syndromic v0.2442 RHEB Zornitza Stark Publications for gene: RHEB were set to
Intellectual disability syndromic and non-syndromic v0.2441 RHEB Zornitza Stark Mode of inheritance for gene: RHEB was changed from Unknown to Other
Intellectual disability syndromic and non-syndromic v0.2440 RHEB Zornitza Stark reviewed gene: RHEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 31337748, 29051493; Phenotypes: Intellectual disability, Macrocephaly, Focal cortical dysplasia; Mode of inheritance: Other
Intellectual disability syndromic and non-syndromic v0.2440 MRPS34 Zornitza Stark Marked gene: MRPS34 as ready
Intellectual disability syndromic and non-syndromic v0.2440 MRPS34 Zornitza Stark Gene: mrps34 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2440 MRPS34 Zornitza Stark Classified gene: MRPS34 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2440 MRPS34 Zornitza Stark Gene: mrps34 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2439 MRPS34 Zornitza Stark gene: MRPS34 was added
gene: MRPS34 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: MRPS34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS34 were set to 28777931
Phenotypes for gene: MRPS34 were set to Combined oxidative phosphorylation deficiency 32, MIM# 617664
Review for gene: MRPS34 was set to GREEN
gene: MRPS34 was marked as current diagnostic
Added comment: Six individuals from 4 unrelated families; clinical presentation is with developmental delay/regression. More variable features include movement disorders, microcephaly, strabismus, nystagmus, optic atrophy.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2438 MIR17HG Zornitza Stark Tag SV/CNV tag was added to gene: MIR17HG.
Intellectual disability syndromic and non-syndromic v0.2438 MIR17HG Zornitza Stark edited their review of gene: MIR17HG: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2438 MFSD2A Zornitza Stark Marked gene: MFSD2A as ready
Intellectual disability syndromic and non-syndromic v0.2438 MFSD2A Zornitza Stark Gene: mfsd2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2438 MFSD2A Zornitza Stark Classified gene: MFSD2A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2438 MFSD2A Zornitza Stark Gene: mfsd2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2437 MFSD2A Zornitza Stark gene: MFSD2A was added
gene: MFSD2A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: MFSD2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MFSD2A were set to 26005865; 26005868; 24828044
Phenotypes for gene: MFSD2A were set to Microcephaly 15, primary, autosomal recessive, MIM# 616486
Review for gene: MFSD2A was set to GREEN
Added comment: Three unrelated families and two animal models.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2436 MED13 Zornitza Stark Marked gene: MED13 as ready
Intellectual disability syndromic and non-syndromic v0.2436 MED13 Zornitza Stark Gene: med13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2436 MED13 Zornitza Stark Phenotypes for gene: MED13 were changed from to Intellectual developmental disorder 61, MIM# 618009
Intellectual disability syndromic and non-syndromic v0.2435 MED13 Zornitza Stark Publications for gene: MED13 were set to
Intellectual disability syndromic and non-syndromic v0.2434 MED13 Zornitza Stark Mode of inheritance for gene: MED13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2433 MED13 Zornitza Stark edited their review of gene: MED13: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.2433 MED13 Zornitza Stark reviewed gene: MED13: Rating: ; Mode of pathogenicity: None; Publications: 29740699; Phenotypes: Intellectual developmental disorder 61, MIM# 618009; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2433 MED12L Zornitza Stark Classified gene: MED12L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2433 MED12L Zornitza Stark Gene: med12l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2432 MED12L Zornitza Stark gene: MED12L was added
gene: MED12L was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: MED12L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MED12L were set to 31155615
Phenotypes for gene: MED12L were set to Intellectual disability; Seizures; Autism
Review for gene: MED12L was set to GREEN
Added comment: 7 individuals reported, 3 with CNVs (encompassing other genes) and 4 with SNVs (frameshift, nonsense and splice site).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2431 MCM3AP Zornitza Stark Marked gene: MCM3AP as ready
Intellectual disability syndromic and non-syndromic v0.2431 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2431 MCM3AP Zornitza Stark Classified gene: MCM3AP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2431 MCM3AP Zornitza Stark Gene: mcm3ap has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2430 MCM3AP Zornitza Stark gene: MCM3AP was added
gene: MCM3AP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, MIM#618124
Review for gene: MCM3AP was set to GREEN
gene: MCM3AP was marked as current diagnostic
Added comment: ID is a feature in many of the reported individuals.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2429 MARS2 Zornitza Stark Classified gene: MARS2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2429 MARS2 Zornitza Stark Gene: mars2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2428 MARS2 Zornitza Stark reviewed gene: MARS2: Rating: RED; Mode of pathogenicity: None; Publications: 25754315; Phenotypes: Combined oxidative phosphorylation deficiency 25, OMIM #616430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2428 MAPRE2 Zornitza Stark Marked gene: MAPRE2 as ready
Intellectual disability syndromic and non-syndromic v0.2428 MAPRE2 Zornitza Stark Gene: mapre2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2428 MAPRE2 Zornitza Stark Classified gene: MAPRE2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2428 MAPRE2 Zornitza Stark Gene: mapre2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2427 MAPRE2 Zornitza Stark gene: MAPRE2 was added
gene: MAPRE2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: MAPRE2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: MAPRE2 were set to 26637975
Phenotypes for gene: MAPRE2 were set to Symmetric circumferential skin creases, congenital, 2, MIM# 616734
Review for gene: MAPRE2 was set to GREEN
Added comment: ID is part of the phenotype, more severe in those with bi-allelic variants.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2426 PURA Zornitza Stark Marked gene: PURA as ready
Intellectual disability syndromic and non-syndromic v0.2426 PURA Zornitza Stark Gene: pura has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2426 PURA Zornitza Stark Phenotypes for gene: PURA were changed from to Mental retardation, autosomal dominant 31, MIM# 616158
Intellectual disability syndromic and non-syndromic v0.2425 PURA Zornitza Stark Publications for gene: PURA were set to
Intellectual disability syndromic and non-syndromic v0.2424 PURA Zornitza Stark Mode of inheritance for gene: PURA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2423 PURA Zornitza Stark reviewed gene: PURA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25439098, 25342064, 12972605; Phenotypes: Mental retardation, autosomal dominant 31, MIM# 616158; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2423 BPTF Zornitza Stark Marked gene: BPTF as ready
Intellectual disability syndromic and non-syndromic v0.2423 BPTF Zornitza Stark Gene: bptf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2423 BPTF Zornitza Stark Phenotypes for gene: BPTF were changed from to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies AD, MIM#617755
Intellectual disability syndromic and non-syndromic v0.2422 BPTF Zornitza Stark Publications for gene: BPTF were set to
Intellectual disability syndromic and non-syndromic v0.2421 BPTF Zornitza Stark Mode of inheritance for gene: BPTF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2420 BPTF Zornitza Stark reviewed gene: BPTF: Rating: GREEN; Mode of pathogenicity: None; Publications: 28942966; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies AD, MIM#617755; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2420 TRIO Zornitza Stark changed review comment from: The nonsense mutations are spread along the TRIO sequence, and affected individuals show variable neurodevelopmental phenotypes. In contrast, missense variants cluster into two mutational hotspots in the TRIO sequence, one in the seventh spectrin repeat and one in the RAC1-activating GEFD1.; to: The nonsense mutations are spread along the TRIO sequence, and affected individuals show variable neurodevelopmental phenotypes. In contrast, missense variants cluster into two mutational hotspots in the TRIO sequence, one in the seventh spectrin repeat and one in the RAC1-activating GEFD1. Individuals with a pathogenic variant in the seventh spectrin repeat have a more severe ID associated with macrocephaly than do most individuals with GEFD1 variants, who display milder ID and microcephaly.
Intellectual disability syndromic and non-syndromic v0.2420 TRIO Zornitza Stark Marked gene: TRIO as ready
Intellectual disability syndromic and non-syndromic v0.2420 TRIO Zornitza Stark Gene: trio has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2420 TRIO Zornitza Stark Phenotypes for gene: TRIO were changed from to Mental retardation, autosomal dominant 44, MIM# 617061
Intellectual disability syndromic and non-syndromic v0.2419 TRIO Zornitza Stark Publications for gene: TRIO were set to
Intellectual disability syndromic and non-syndromic v0.2418 TRIO Zornitza Stark Mode of inheritance for gene: TRIO was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2417 TRIO Zornitza Stark reviewed gene: TRIO: Rating: GREEN; Mode of pathogenicity: None; Publications: 26721934, 32109419; Phenotypes: Mental retardation, autosomal dominant 44, MIM# 617061; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2417 MAN1B1 Zornitza Stark Marked gene: MAN1B1 as ready
Intellectual disability syndromic and non-syndromic v0.2417 MAN1B1 Zornitza Stark Gene: man1b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2417 MAN1B1 Zornitza Stark Phenotypes for gene: MAN1B1 were changed from to Mental retardation, autosomal recessive 15, MIM#614202
Intellectual disability syndromic and non-syndromic v0.2416 MAN1B1 Zornitza Stark Mode of inheritance for gene: MAN1B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2415 MAN1B1 Zornitza Stark reviewed gene: MAN1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive 15, MIM#614202; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2415 KMT2C Zornitza Stark Marked gene: KMT2C as ready
Intellectual disability syndromic and non-syndromic v0.2415 KMT2C Zornitza Stark Gene: kmt2c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2415 KMT2C Zornitza Stark Phenotypes for gene: KMT2C were changed from to Kleefstra syndrome 2, MIM#617768
Intellectual disability syndromic and non-syndromic v0.2414 KMT2C Zornitza Stark Mode of inheritance for gene: KMT2C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2413 KMT2C Zornitza Stark reviewed gene: KMT2C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kleefstra syndrome 2, MIM#617768; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2413 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2413 NUP188 Zornitza Stark changed review comment from: Two unrelated individuals with homozygous truncating variants in this gene reported, Sandestin et al 2019, plus another by Strauss et al 2018. Also note two papers reporting mono allelic variants and disparate phenotypes (CDH and mitral valve prolapse, respectively), Yates et al, Haskell et al.; to: Two unrelated individuals with homozygous truncating variants in this gene reported, Sandestig et al 2019 (died in early infancy), plus another by Strauss et al 2018. Also note two papers reporting mono allelic variants and disparate phenotypes (CDH and mitral valve prolapse, respectively), Yates et al, Haskell et al.
Intellectual disability syndromic and non-syndromic v0.2413 NUP188 Zornitza Stark edited their review of gene: NUP188: Changed publications: 32021605, 28726809
Intellectual disability syndromic and non-syndromic v0.2413 NUDT2 Zornitza Stark Marked gene: NUDT2 as ready
Intellectual disability syndromic and non-syndromic v0.2413 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2413 NUDT2 Zornitza Stark Classified gene: NUDT2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2413 NUDT2 Zornitza Stark Gene: nudt2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2412 NUDT2 Zornitza Stark gene: NUDT2 was added
gene: NUDT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to 27431290; 30059600
Phenotypes for gene: NUDT2 were set to Muscular hypotonia; Global developmental delay; Intellectual disability
Review for gene: NUDT2 was set to AMBER
Added comment: 7 affected individuals from 4 Saudi families, with same homozygous truncating variant.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2411 NPHP3 Zornitza Stark reviewed gene: NPHP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18371931; Phenotypes: Meckel syndrome 7, MIM# 267010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2411 NKAP Zornitza Stark Marked gene: NKAP as ready
Intellectual disability syndromic and non-syndromic v0.2411 NKAP Zornitza Stark Gene: nkap has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2411 NKAP Zornitza Stark Classified gene: NKAP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2411 NKAP Zornitza Stark Gene: nkap has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2410 NKAP Zornitza Stark gene: NKAP was added
gene: NKAP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: NKAP was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: NKAP were set to 26358559; 26350204; 31587868
Phenotypes for gene: NKAP were set to Intellectual disability
Review for gene: NKAP was set to GREEN
gene: NKAP was marked as current diagnostic
Added comment: 10 males from 8 unrelated families with missense variants in NKAP. Main features: intellectual disability, hypotonia, tall stature with Marfanoid habitus. Recurrent variant (NM_024528:c.988G>A / p.Arg333Gln) seen in several families from different ethnic backgrounds.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2409 NHP2 Zornitza Stark Marked gene: NHP2 as ready
Intellectual disability syndromic and non-syndromic v0.2409 NHP2 Zornitza Stark Gene: nhp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2409 NHP2 Zornitza Stark Phenotypes for gene: NHP2 were changed from to Dyskeratosis congenita, autosomal recessive 2, MIM# 613987; Høyeraal-Hreidarsson syndrome
Intellectual disability syndromic and non-syndromic v0.2408 NHP2 Zornitza Stark Publications for gene: NHP2 were set to
Intellectual disability syndromic and non-syndromic v0.2407 NHP2 Zornitza Stark Mode of inheritance for gene: NHP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2406 NHP2 Zornitza Stark Classified gene: NHP2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2406 NHP2 Zornitza Stark Gene: nhp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2405 NHP2 Zornitza Stark reviewed gene: NHP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 18523010, 31985013; Phenotypes: Dyskeratosis congenita, autosomal recessive 2, MIM# 613987, Høyeraal-Hreidarsson syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2405 NHEJ1 Zornitza Stark Marked gene: NHEJ1 as ready
Intellectual disability syndromic and non-syndromic v0.2405 NHEJ1 Zornitza Stark Gene: nhej1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2405 NHEJ1 Zornitza Stark Phenotypes for gene: NHEJ1 were changed from to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM#611291
Intellectual disability syndromic and non-syndromic v0.2404 NHEJ1 Zornitza Stark Publications for gene: NHEJ1 were set to
Intellectual disability syndromic and non-syndromic v0.2403 NHEJ1 Zornitza Stark Mode of inheritance for gene: NHEJ1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2402 NHEJ1 Zornitza Stark Classified gene: NHEJ1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2402 NHEJ1 Zornitza Stark Gene: nhej1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2401 NHEJ1 Zornitza Stark reviewed gene: NHEJ1: Rating: RED; Mode of pathogenicity: None; Publications: 16439204; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM#611291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2401 NGF Zornitza Stark Marked gene: NGF as ready
Intellectual disability syndromic and non-syndromic v0.2401 NGF Zornitza Stark Gene: ngf has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2401 NGF Zornitza Stark Phenotypes for gene: NGF were changed from to Neuropathy, hereditary sensory and autonomic, type V, MIM# 608654
Intellectual disability syndromic and non-syndromic v0.2400 NGF Zornitza Stark Mode of inheritance for gene: NGF was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2399 NGF Zornitza Stark Classified gene: NGF as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2399 NGF Zornitza Stark Gene: ngf has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2398 NGF Zornitza Stark reviewed gene: NGF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type V, MIM# 608654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2398 NDUFV2 Zornitza Stark Classified gene: NDUFV2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2398 NDUFV2 Zornitza Stark Gene: ndufv2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2397 NDUFV2 Zornitza Stark changed review comment from: Multiple unrelated families.; to: Multiple unrelated families. Common presenting features include HOCM and encephalopathy, unclear in what proportion ID is likely to be the presenting or main feature.
Intellectual disability syndromic and non-syndromic v0.2397 NDUFV2 Zornitza Stark edited their review of gene: NDUFV2: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2397 NDUFS6 Zornitza Stark Classified gene: NDUFS6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2397 NDUFS6 Zornitza Stark Gene: ndufs6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2396 NDUFS6 Zornitza Stark changed review comment from: Multiple affected families, functional data.; to: Multiple affected families, functional data. Limited clinical information in some reports. In some families, the presentation has been with severe neonatal lactic acidosis, therefore difficult to be sure in what proportion ID is likely to be the presenting or main feature.
Intellectual disability syndromic and non-syndromic v0.2396 NDUFS6 Zornitza Stark edited their review of gene: NDUFS6: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2396 NDUFS3 Zornitza Stark Classified gene: NDUFS3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2396 NDUFS3 Zornitza Stark Gene: ndufs3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2395 NDUFS3 Zornitza Stark changed review comment from: At least three families reported.; to: At least three families reported. In the original report, the affected individual was phenotypically normal until 9 years of age but had rapidly progressive multi-system disease.
Intellectual disability syndromic and non-syndromic v0.2395 NDUFS3 Zornitza Stark edited their review of gene: NDUFS3: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2395 NDUFS2 Zornitza Stark Classified gene: NDUFS2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2395 NDUFS2 Zornitza Stark Gene: ndufs2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2394 NDUFS2 Zornitza Stark changed review comment from: Multiple unrelated families. Phenotype in one family was more consistent with regression; in another family severe neonatal lactic acidosis led to death in the first few days of life; and in the third family presentation was with failure to thrive, vomiting, nystagmus, and specifically normal cognition despite delayed motor milestones due to hypotonia. Limited clinical information reported in other papers therefore difficult to know whether ID is likely to be the presenting or main feature of this mitochondrial disorder..; to: Multiple unrelated families. Phenotype in one family was more consistent with regression; in another family severe neonatal lactic acidosis led to death in the first few days of life; and in the third family presentation was with failure to thrive, vomiting, nystagmus, and specifically normal cognition despite delayed motor milestones due to hypotonia. Limited clinical information reported in other papers therefore difficult to know whether ID is likely to be the presenting or main feature of this mitochondrial disorder.
Intellectual disability syndromic and non-syndromic v0.2394 NDUFS2 Zornitza Stark changed review comment from: Multiple unrelated families.; to: Multiple unrelated families. Phenotype in one family was more consistent with regression; in another family severe neonatal lactic acidosis led to death in the first few days of life; and in the third family presentation was with failure to thrive, vomiting, nystagmus, and specifically normal cognition despite delayed motor milestones due to hypotonia. Limited clinical information reported in other papers therefore difficult to know whether ID is likely to be the presenting or main feature of this mitochondrial disorder..
Intellectual disability syndromic and non-syndromic v0.2394 NDUFS2 Zornitza Stark edited their review of gene: NDUFS2: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2394 TBR1 Zornitza Stark Marked gene: TBR1 as ready
Intellectual disability syndromic and non-syndromic v0.2394 TBR1 Zornitza Stark Gene: tbr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2394 TBR1 Zornitza Stark Phenotypes for gene: TBR1 were changed from to Intellectual developmental disorder with autism and speech delay, MIM# 606053
Intellectual disability syndromic and non-syndromic v0.2393 TBR1 Zornitza Stark Publications for gene: TBR1 were set to
Intellectual disability syndromic and non-syndromic v0.2392 TBR1 Zornitza Stark Mode of inheritance for gene: TBR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2391 TBR1 Zornitza Stark reviewed gene: TBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25232744, 30250039; Phenotypes: Intellectual developmental disorder with autism and speech delay, MIM# 606053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2391 NDUFS1 Zornitza Stark Marked gene: NDUFS1 as ready
Intellectual disability syndromic and non-syndromic v0.2391 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2391 NDUFS1 Zornitza Stark Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226 to Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226
Intellectual disability syndromic and non-syndromic v0.2390 NDUFS1 Zornitza Stark Phenotypes for gene: NDUFS1 were changed from to Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226
Intellectual disability syndromic and non-syndromic v0.2390 NDUFS1 Zornitza Stark Publications for gene: NDUFS1 were set to 20382551
Intellectual disability syndromic and non-syndromic v0.2390 NDUFS1 Zornitza Stark Publications for gene: NDUFS1 were set to
Intellectual disability syndromic and non-syndromic v0.2389 NDUFS1 Zornitza Stark Mode of inheritance for gene: NDUFS1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2389 NDUFS1 Zornitza Stark Mode of inheritance for gene: NDUFS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2388 NDUFS1 Zornitza Stark reviewed gene: NDUFS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20382551; Phenotypes: Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2388 NDUFB3 Zornitza Stark Classified gene: NDUFB3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2388 NDUFB3 Zornitza Stark Gene: ndufb3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2387 NDUFB3 Zornitza Stark changed review comment from: Ten families and functional data.; to: Ten families and functional data. In particular, the 8 families of shared Irish ancestry only had short stature and dysmorphic features, without marked metabolic disturbance. One of the other reported individuals died in infancy, again making it difficult to know whether ID would have been part of the phenotype.
Intellectual disability syndromic and non-syndromic v0.2387 NDUFB3 Zornitza Stark edited their review of gene: NDUFB3: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2387 NDUFAF6 Zornitza Stark Classified gene: NDUFAF6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2387 NDUFAF6 Zornitza Stark Gene: ndufaf6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2386 NDUFAF6 Zornitza Stark changed review comment from: Multiple unrelated families reported.; to: Multiple unrelated families reported. Presentation in one family was with lactic acidosis in newborn period, and in another with regression in childhood. Limited phenotypic information for others. Unclear if and in what proportion of affected individuals ID is likely to be the main or presenting feature.
Intellectual disability syndromic and non-syndromic v0.2386 NDUFAF6 Zornitza Stark edited their review of gene: NDUFAF6: Changed rating: AMBER; Changed publications: 26741492, 18614015, 27623250
Intellectual disability syndromic and non-syndromic v0.2386 NDUFAF5 Zornitza Stark Marked gene: NDUFAF5 as ready
Intellectual disability syndromic and non-syndromic v0.2386 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2386 NDUFAF5 Zornitza Stark Phenotypes for gene: NDUFAF5 were changed from to Mitochondrial complex I deficiency, nuclear type 16, MIM# 618238
Intellectual disability syndromic and non-syndromic v0.2385 NDUFAF5 Zornitza Stark Publications for gene: NDUFAF5 were set to
Intellectual disability syndromic and non-syndromic v0.2384 NDUFAF5 Zornitza Stark Mode of inheritance for gene: NDUFAF5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2383 NDUFAF5 Zornitza Stark Classified gene: NDUFAF5 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2383 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2382 NDUFAF5 Zornitza Stark reviewed gene: NDUFAF5: Rating: AMBER; Mode of pathogenicity: None; Publications: 19542079, 21607760, 18940309; Phenotypes: Mitochondrial complex I deficiency, nuclear type 16, MIM# 618238; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2382 NDUFAF4 Zornitza Stark Classified gene: NDUFAF4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2382 NDUFAF4 Zornitza Stark Gene: ndufaf4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2381 NDUFAF4 Zornitza Stark changed review comment from: Two unrelated families and functional data.; to: Two unrelated families and functional data. Multiple affected individuals in one family (18179882) presented in newborn period with marked lactic acidosis, one long-term survivor (7yo at assessment) had profound ID. Individual from second family (28853723) presented in infancy with dev delay. Borderline gene-disease association for mitochondrial disease, and unclear what proportion of individuals are likely to present/manifest as ID.
Intellectual disability syndromic and non-syndromic v0.2381 NDUFAF4 Zornitza Stark edited their review of gene: NDUFAF4: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2381 NDUFAF3 Zornitza Stark Classified gene: NDUFAF3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2381 NDUFAF3 Zornitza Stark Gene: ndufaf3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2380 NDUFAF3 Zornitza Stark changed review comment from: Three unrelated families reported.; to: Three unrelated families reported, severe neonatal presentation with lactic acidosis, seizures, and need for respiratory support. ID is unlikely to be the presenting or main feature.
Intellectual disability syndromic and non-syndromic v0.2380 NDUFAF3 Zornitza Stark edited their review of gene: NDUFAF3: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2380 NDUFAF2 Zornitza Stark Classified gene: NDUFAF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2380 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2379 NDUFAF2 Zornitza Stark changed review comment from: At least four unrelated families reported.; to: At least four unrelated families reported, complex neurological presentation with optic atrophy, nystagmus, ataxia in some, others described as ventilator-dependent. ID is unlikely to be the presenting or main feature.
Intellectual disability syndromic and non-syndromic v0.2379 NDUFAF2 Zornitza Stark edited their review of gene: NDUFAF2: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2379 NDUFAF2 Zornitza Stark edited their review of gene: NDUFAF2: Changed publications: 20571988
Intellectual disability syndromic and non-syndromic v0.2379 NDUFAF1 Zornitza Stark changed review comment from: Three unrelated families described, DD/ID part of the phenotype.; to: Three unrelated families described, DD/ID part of the phenotype, specifically mentioned in two families, child in third family died in infancy from HOCM.
Intellectual disability syndromic and non-syndromic v0.2379 NDUFA9 Zornitza Stark Classified gene: NDUFA9 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2379 NDUFA9 Zornitza Stark Gene: ndufa9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2378 NDUFA9 Zornitza Stark changed review comment from: Two unrelated families and functional data. Broad spectrum, likely to include ID.; to: Two unrelated families and functional data. Broad spectrum, likely to include ID but that is yet to be established.
Intellectual disability syndromic and non-syndromic v0.2378 NDUFA9 Zornitza Stark edited their review of gene: NDUFA9: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2378 NDUFA10 Zornitza Stark Classified gene: NDUFA10 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2378 NDUFA10 Zornitza Stark Gene: ndufa10 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2377 NDUFA10 Zornitza Stark Deleted their comment
Intellectual disability syndromic and non-syndromic v0.2377 NDUFA10 Zornitza Stark edited their review of gene: NDUFA10: Added comment: Two families, functional data, but phenotypic description only available for one (DD/ID part of the phenotype).; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2377 SYNGAP1 Zornitza Stark Marked gene: SYNGAP1 as ready
Intellectual disability syndromic and non-syndromic v0.2377 SYNGAP1 Zornitza Stark Gene: syngap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2377 SYNGAP1 Zornitza Stark Phenotypes for gene: SYNGAP1 were changed from to Intellectual disability, autosomal dominant 5 (MIM # 612621)
Intellectual disability syndromic and non-syndromic v0.2376 SYNGAP1 Zornitza Stark Publications for gene: SYNGAP1 were set to
Intellectual disability syndromic and non-syndromic v0.2375 SYNGAP1 Zornitza Stark Mode of inheritance for gene: SYNGAP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2374 NBN Zornitza Stark Marked gene: NBN as ready
Intellectual disability syndromic and non-syndromic v0.2374 NBN Zornitza Stark Gene: nbn has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2374 NBN Zornitza Stark Phenotypes for gene: NBN were changed from to Nijmegen breakage syndrome, MIM# 251260
Intellectual disability syndromic and non-syndromic v0.2373 NBN Zornitza Stark Mode of inheritance for gene: NBN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2372 NBN Zornitza Stark Classified gene: NBN as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2372 NBN Zornitza Stark Gene: nbn has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2371 NBN Zornitza Stark reviewed gene: NBN: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Nijmegen breakage syndrome, MIM# 251260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2371 SYNGAP1 Ain Roesley reviewed gene: SYNGAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26079862; Phenotypes: Intellectual disability, autosomal dominant 5 (MIM # 612621); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2371 ZBTB24 Zornitza Stark Marked gene: ZBTB24 as ready
Intellectual disability syndromic and non-syndromic v0.2371 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2371 ZBTB24 Zornitza Stark Phenotypes for gene: ZBTB24 were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 2; OMIM # 614069
Intellectual disability syndromic and non-syndromic v0.2370 ZBTB24 Zornitza Stark Publications for gene: ZBTB24 were set to
Intellectual disability syndromic and non-syndromic v0.2369 ZBTB24 Zornitza Stark Mode of inheritance for gene: ZBTB24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2368 ZBTB16 Zornitza Stark Marked gene: ZBTB16 as ready
Intellectual disability syndromic and non-syndromic v0.2368 ZBTB16 Zornitza Stark Gene: zbtb16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2368 ZBTB16 Zornitza Stark Phenotypes for gene: ZBTB16 were changed from to Skeletal defects, genital hypoplasia, and mental retardation, OMIM #612447
Intellectual disability syndromic and non-syndromic v0.2367 ZBTB16 Zornitza Stark Publications for gene: ZBTB16 were set to
Intellectual disability syndromic and non-syndromic v0.2366 ZBTB16 Zornitza Stark Mode of inheritance for gene: ZBTB16 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2365 ZBTB11 Zornitza Stark Marked gene: ZBTB11 as ready
Intellectual disability syndromic and non-syndromic v0.2365 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2365 ZBTB11 Zornitza Stark Phenotypes for gene: ZBTB11 were changed from to Intellectual developmental disorder, autosomal recessive 69; OMIM #618383
Intellectual disability syndromic and non-syndromic v0.2364 ZBTB11 Zornitza Stark Publications for gene: ZBTB11 were set to
Intellectual disability syndromic and non-syndromic v0.2363 ZBTB11 Zornitza Stark Mode of inheritance for gene: ZBTB11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2362 XPA Zornitza Stark Publications for gene: XPA were set to
Intellectual disability syndromic and non-syndromic v0.2361 XPA Zornitza Stark reviewed gene: XPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 26302748, 25566891, 24135642; Phenotypes: Xeroderma pigmentosum, group A, OMIM# 278700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2361 WNT5A Zornitza Stark reviewed gene: WNT5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 17256787; Phenotypes: Robinow syndrome, autosomal dominant 1, OMIM# 180700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2361 WFS1 Zornitza Stark Phenotypes for gene: WFS1 were changed from to Wolfram syndrome 1, MIM# 222300; Wolfram-like syndrome, autosomal dominant, MIM# 614296
Intellectual disability syndromic and non-syndromic v0.2360 WFS1 Zornitza Stark Mode of inheritance for gene: WFS1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2359 WFS1 Zornitza Stark Classified gene: WFS1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2359 WFS1 Zornitza Stark Gene: wfs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2358 WFS1 Zornitza Stark reviewed gene: WFS1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Wolfram syndrome 1, MIM# 222300, Wolfram-like syndrome, autosomal dominant, MIM# 614296; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2358 WDR81 Zornitza Stark Marked gene: WDR81 as ready
Intellectual disability syndromic and non-syndromic v0.2358 WDR81 Zornitza Stark Gene: wdr81 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2358 WDR81 Zornitza Stark Phenotypes for gene: WDR81 were changed from to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185; Hydrocephalus, congenital, 3, with brain anomalies, 617967
Intellectual disability syndromic and non-syndromic v0.2357 WDR81 Zornitza Stark Publications for gene: WDR81 were set to
Intellectual disability syndromic and non-syndromic v0.2356 WDR81 Zornitza Stark Mode of inheritance for gene: WDR81 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2355 WDR4 Zornitza Stark Marked gene: WDR4 as ready
Intellectual disability syndromic and non-syndromic v0.2355 WDR4 Zornitza Stark Added comment: Comment when marking as ready: Borderline Green rating: three families but two have the same homozygous variant; some functional data to support gene-disease association.
Intellectual disability syndromic and non-syndromic v0.2355 WDR4 Zornitza Stark Gene: wdr4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2355 WDR4 Zornitza Stark Marked gene: WDR4 as ready
Intellectual disability syndromic and non-syndromic v0.2355 WDR4 Zornitza Stark Gene: wdr4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2355 WDR4 Zornitza Stark Publications for gene: WDR4 were set to PubMed: 26416026, 30079490, 29597095, 28617965
Intellectual disability syndromic and non-syndromic v0.2354 VARS Zornitza Stark Marked gene: VARS as ready
Intellectual disability syndromic and non-syndromic v0.2354 VARS Zornitza Stark Gene: vars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2354 VARS Zornitza Stark Publications for gene: VARS were set to PubMed: 30755616, 30755602, 26539891, 29691655, 30275004
Intellectual disability syndromic and non-syndromic v0.2353 TXNL4A Zornitza Stark Marked gene: TXNL4A as ready
Intellectual disability syndromic and non-syndromic v0.2353 TXNL4A Zornitza Stark Gene: txnl4a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2353 TXNL4A Zornitza Stark Phenotypes for gene: TXNL4A were changed from to Burn-McKeown syndrome, MIM# 608572
Intellectual disability syndromic and non-syndromic v0.2352 TXNL4A Zornitza Stark Mode of inheritance for gene: TXNL4A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2351 TXNL4A Zornitza Stark Classified gene: TXNL4A as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2351 TXNL4A Zornitza Stark Gene: txnl4a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2350 TXNL4A Zornitza Stark reviewed gene: TXNL4A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Burn-McKeown syndrome, MIM# 608572; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2350 TUBGCP4 Zornitza Stark Marked gene: TUBGCP4 as ready
Intellectual disability syndromic and non-syndromic v0.2350 TUBGCP4 Zornitza Stark Gene: tubgcp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2350 TUBGCP4 Zornitza Stark Classified gene: TUBGCP4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2350 TUBGCP4 Zornitza Stark Gene: tubgcp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2349 TUBGCP4 Zornitza Stark gene: TUBGCP4 was added
gene: TUBGCP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TUBGCP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP4 were set to 25817018
Phenotypes for gene: TUBGCP4 were set to Microcephaly and chorioretinopathy, autosomal recessive, 3, 616335
Review for gene: TUBGCP4 was set to AMBER
Added comment: Three unrelated families reported; ID described as mild.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2348 TUBA8 Zornitza Stark Phenotypes for gene: TUBA8 were changed from to Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180
Intellectual disability syndromic and non-syndromic v0.2347 TUBA8 Zornitza Stark Publications for gene: TUBA8 were set to
Intellectual disability syndromic and non-syndromic v0.2346 TUBA8 Zornitza Stark Mode of inheritance for gene: TUBA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2345 TUBA8 Zornitza Stark Classified gene: TUBA8 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2345 TUBA8 Zornitza Stark Gene: tuba8 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2344 TUBA8 Zornitza Stark reviewed gene: TUBA8: Rating: RED; Mode of pathogenicity: None; Publications: 19896110, 31481326, 28388629; Phenotypes: Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2344 TSHR Zornitza Stark Marked gene: TSHR as ready
Intellectual disability syndromic and non-syndromic v0.2344 TSHR Zornitza Stark Gene: tshr has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2344 TSHR Zornitza Stark Phenotypes for gene: TSHR were changed from to Hypothyroidism, congenital, nongoitrous, 1, MIM# 275200
Intellectual disability syndromic and non-syndromic v0.2343 TSHR Zornitza Stark Mode of inheritance for gene: TSHR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2342 TSHR Zornitza Stark Mode of inheritance for gene: TSHR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2341 TSHR Zornitza Stark Classified gene: TSHR as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2341 TSHR Zornitza Stark Gene: tshr has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2340 TSHR Zornitza Stark reviewed gene: TSHR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypothyroidism, congenital, nongoitrous, 1, MIM# 275200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2340 TSEN15 Zornitza Stark Marked gene: TSEN15 as ready
Intellectual disability syndromic and non-syndromic v0.2340 TSEN15 Zornitza Stark Gene: tsen15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2340 TSEN15 Zornitza Stark Classified gene: TSEN15 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2340 TSEN15 Zornitza Stark Gene: tsen15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2339 TSEN15 Zornitza Stark gene: TSEN15 was added
gene: TSEN15 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TSEN15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN15 were set to 27392077; 30914295; 25558065
Phenotypes for gene: TSEN15 were set to Pontocerebellar hypoplasia, type 2F, 617026
Review for gene: TSEN15 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2338 TRIP13 Zornitza Stark Marked gene: TRIP13 as ready
Intellectual disability syndromic and non-syndromic v0.2338 TRIP13 Zornitza Stark Gene: trip13 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2338 TRIP13 Zornitza Stark Phenotypes for gene: TRIP13 were changed from to Mosaic variegated aneuploidy syndrome 3, MIM# 617598
Intellectual disability syndromic and non-syndromic v0.2337 TRIP13 Zornitza Stark Publications for gene: TRIP13 were set to
Intellectual disability syndromic and non-syndromic v0.2336 TRIP13 Zornitza Stark Mode of inheritance for gene: TRIP13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2335 TRIP13 Zornitza Stark Classified gene: TRIP13 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2335 TRIP13 Zornitza Stark Gene: trip13 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2334 TRIP13 Zornitza Stark reviewed gene: TRIP13: Rating: AMBER; Mode of pathogenicity: None; Publications: 28553959; Phenotypes: Mosaic variegated aneuploidy syndrome 3, MIM# 617598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2334 TRIM8 Zornitza Stark changed review comment from: Six unrelated individuals reported.
Sources: Expert list; to: Six unrelated individuals reported. All variants reported to date are truncating, affecting the last (sixth exon) and as a result may escape nonsense-mediated decay. Since TRIM8 homodimerizes via its (upstream) coiled-coil domain and its C-terminal domain is required for nuclear localization, a dominant-negative effect is postulated by the authors. Haploinsufficiency appears less likely.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2334 TRIM8 Zornitza Stark Marked gene: TRIM8 as ready
Intellectual disability syndromic and non-syndromic v0.2334 TRIM8 Zornitza Stark Gene: trim8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2334 TRIM8 Zornitza Stark Classified gene: TRIM8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2334 TRIM8 Zornitza Stark Gene: trim8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2333 TRIM8 Zornitza Stark gene: TRIM8 was added
gene: TRIM8 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TRIM8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM8 were set to 30244534; 27346735; 23934111
Phenotypes for gene: TRIM8 were set to Intellectual disability; Seizures
Review for gene: TRIM8 was set to GREEN
gene: TRIM8 was marked as current diagnostic
Added comment: Six unrelated individuals reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2332 TRAK1 Zornitza Stark Marked gene: TRAK1 as ready
Intellectual disability syndromic and non-syndromic v0.2332 TRAK1 Zornitza Stark Gene: trak1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2332 TRAK1 Zornitza Stark Phenotypes for gene: TRAK1 were changed from to Epileptic encephalopathy, early infantile, 68, MIM# 618201
Intellectual disability syndromic and non-syndromic v0.2331 TRAK1 Zornitza Stark Publications for gene: TRAK1 were set to
Intellectual disability syndromic and non-syndromic v0.2330 TRAK1 Zornitza Stark Mode of inheritance for gene: TRAK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2329 TRAK1 Zornitza Stark reviewed gene: TRAK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 28364549, 29846532; Phenotypes: Epileptic encephalopathy, early infantile, 68, MIM# 618201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2329 TRAIP Zornitza Stark Marked gene: TRAIP as ready
Intellectual disability syndromic and non-syndromic v0.2329 TRAIP Zornitza Stark Gene: traip has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2329 TRAIP Zornitza Stark Classified gene: TRAIP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2329 TRAIP Zornitza Stark Gene: traip has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2328 TRAIP Zornitza Stark gene: TRAIP was added
gene: TRAIP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TRAIP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAIP were set to Seckel syndrome 9, MIM#616777
Review for gene: TRAIP was set to GREEN
gene: TRAIP was marked as current diagnostic
Added comment: Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2327 TPK1 Zornitza Stark Marked gene: TPK1 as ready
Intellectual disability syndromic and non-syndromic v0.2327 TPK1 Zornitza Stark Gene: tpk1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2327 TPK1 Zornitza Stark Phenotypes for gene: TPK1 were changed from to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type), MIM# 614458
Intellectual disability syndromic and non-syndromic v0.2326 TPK1 Zornitza Stark Mode of inheritance for gene: TPK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2325 TPK1 Zornitza Stark Classified gene: TPK1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2325 TPK1 Zornitza Stark Gene: tpk1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2324 TPK1 Zornitza Stark reviewed gene: TPK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type), MIM# 614458; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2324 TPH2 Zornitza Stark Marked gene: TPH2 as ready
Intellectual disability syndromic and non-syndromic v0.2324 TPH2 Zornitza Stark Gene: tph2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2324 TPH2 Zornitza Stark Phenotypes for gene: TPH2 were changed from to {Attention deficit-hyperactivity disorder, susceptibility to, 7} 613003
Intellectual disability syndromic and non-syndromic v0.2323 TPH2 Zornitza Stark Publications for gene: TPH2 were set to
Intellectual disability syndromic and non-syndromic v0.2322 TPH2 Zornitza Stark Mode of inheritance for gene: TPH2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2321 TPH2 Zornitza Stark Classified gene: TPH2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2321 TPH2 Zornitza Stark Gene: tph2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2320 TPH2 Zornitza Stark reviewed gene: TPH2: Rating: RED; Mode of pathogenicity: None; Publications: 18347598; Phenotypes: {Attention deficit-hyperactivity disorder, susceptibility to, 7} 613003; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2320 SPOP Zornitza Stark Marked gene: SPOP as ready
Intellectual disability syndromic and non-syndromic v0.2320 SPOP Zornitza Stark Gene: spop has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2320 SPOP Zornitza Stark Classified gene: SPOP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2320 SPOP Zornitza Stark Gene: spop has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2319 SPOP Zornitza Stark gene: SPOP was added
gene: SPOP was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SPOP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPOP were set to 32109420
Phenotypes for gene: SPOP were set to Intellectual disability; dysmorphism; microcephaly; macrocephaly
Mode of pathogenicity for gene: SPOP was set to Other
Review for gene: SPOP was set to GREEN
Added comment: Seven individuals reported with de novo missense variants in this gene. Gain-of-function variants associated with microcephaly whereas dominant-negative variants associated with macrocephaly.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2318 TNIK Zornitza Stark Marked gene: TNIK as ready
Intellectual disability syndromic and non-syndromic v0.2318 TNIK Zornitza Stark Gene: tnik has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2318 TNIK Zornitza Stark Phenotypes for gene: TNIK were changed from to Mental retardation, autosomal recessive 54, MIM# 617028
Intellectual disability syndromic and non-syndromic v0.2317 TNIK Zornitza Stark Publications for gene: TNIK were set to
Intellectual disability syndromic and non-syndromic v0.2316 TNIK Zornitza Stark Mode of inheritance for gene: TNIK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2315 TNIK Zornitza Stark Classified gene: TNIK as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2315 TNIK Zornitza Stark Gene: tnik has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2314 TNIK Zornitza Stark reviewed gene: TNIK: Rating: AMBER; Mode of pathogenicity: None; Publications: 27106596, 23035106; Phenotypes: Mental retardation, autosomal recessive 54, MIM# 617028; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2314 TMLHE Zornitza Stark Marked gene: TMLHE as ready
Intellectual disability syndromic and non-syndromic v0.2314 TMLHE Zornitza Stark Gene: tmlhe has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2314 TMLHE Zornitza Stark Phenotypes for gene: TMLHE were changed from to {Autism, susceptibility to, X-linked 6} 300872
Intellectual disability syndromic and non-syndromic v0.2313 TMLHE Zornitza Stark Publications for gene: TMLHE were set to 21865298
Intellectual disability syndromic and non-syndromic v0.2313 TMLHE Zornitza Stark Publications for gene: TMLHE were set to
Intellectual disability syndromic and non-syndromic v0.2312 TMLHE Zornitza Stark Mode of inheritance for gene: TMLHE was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2311 TMLHE Zornitza Stark Classified gene: TMLHE as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2311 TMLHE Zornitza Stark Gene: tmlhe has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2310 TMLHE Zornitza Stark reviewed gene: TMLHE: Rating: AMBER; Mode of pathogenicity: None; Publications: 21865298; Phenotypes: {Autism, susceptibility to, X-linked 6} 300872; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2310 TMEM94 Zornitza Stark Marked gene: TMEM94 as ready
Intellectual disability syndromic and non-syndromic v0.2310 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2310 TMEM94 Zornitza Stark Classified gene: TMEM94 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2310 TMEM94 Zornitza Stark Gene: tmem94 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2309 TMEM94 Zornitza Stark gene: TMEM94 was added
gene: TMEM94 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM94 were set to 30526868
Phenotypes for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies, MIM#618316
Review for gene: TMEM94 was set to GREEN
Added comment: 10 individuals from 6 unrelated families.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2308 TMEM260 Zornitza Stark Marked gene: TMEM260 as ready
Intellectual disability syndromic and non-syndromic v0.2308 TMEM260 Zornitza Stark Gene: tmem260 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2308 TMEM260 Zornitza Stark Phenotypes for gene: TMEM260 were changed from to Structural heart defects and renal anomalies syndrome, MIM# 617478
Intellectual disability syndromic and non-syndromic v0.2307 TMEM260 Zornitza Stark Publications for gene: TMEM260 were set to
Intellectual disability syndromic and non-syndromic v0.2306 TMEM260 Zornitza Stark Mode of inheritance for gene: TMEM260 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2305 TMEM260 Zornitza Stark Classified gene: TMEM260 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2305 TMEM260 Zornitza Stark Gene: tmem260 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2304 TMEM260 Zornitza Stark reviewed gene: TMEM260: Rating: RED; Mode of pathogenicity: None; Publications: 28318500; Phenotypes: Structural heart defects and renal anomalies syndrome, MIM# 617478; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2304 TKT Zornitza Stark Classified gene: TKT as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2304 TKT Zornitza Stark Gene: tkt has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2303 TKT Zornitza Stark reviewed gene: TKT: Rating: AMBER; Mode of pathogenicity: None; Publications: 27259054; Phenotypes: Short stature, developmental delay, and congenital heart defects, OMIM #617044; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2303 TINF2 Zornitza Stark Marked gene: TINF2 as ready
Intellectual disability syndromic and non-syndromic v0.2303 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2303 TINF2 Zornitza Stark Phenotypes for gene: TINF2 were changed from to Revesz syndrome, MIM# 268130
Intellectual disability syndromic and non-syndromic v0.2302 TINF2 Zornitza Stark Publications for gene: TINF2 were set to
Intellectual disability syndromic and non-syndromic v0.2301 TINF2 Zornitza Stark Mode of inheritance for gene: TINF2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2300 TINF2 Zornitza Stark reviewed gene: TINF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1404302, 18252230, 21477109; Phenotypes: Revesz syndrome, MIM# 268130; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2300 TIMM50 Zornitza Stark Marked gene: TIMM50 as ready
Intellectual disability syndromic and non-syndromic v0.2300 TIMM50 Zornitza Stark Gene: timm50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2300 TIMM50 Zornitza Stark Classified gene: TIMM50 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2300 TIMM50 Zornitza Stark Gene: timm50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2299 TIMM50 Zornitza Stark gene: TIMM50 was added
gene: TIMM50 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TIMM50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TIMM50 were set to 27573165; 30190335; 31058414
Phenotypes for gene: TIMM50 were set to 3-methylglutaconic aciduria, type IX, MIM#617698
Review for gene: TIMM50 was set to GREEN
Added comment: Four unrelated families reported, ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2298 THRB Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: ID is not generally part of the phenotype but a couple of more severe presentations including ID reported.
Intellectual disability syndromic and non-syndromic v0.2298 THRB Zornitza Stark edited their review of gene: THRB: Changed rating: AMBER; Changed publications: 22319036, 1682340
Intellectual disability syndromic and non-syndromic v0.2298 THRB Zornitza Stark Marked gene: THRB as ready
Intellectual disability syndromic and non-syndromic v0.2298 THRB Zornitza Stark Gene: thrb has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2298 THRB Zornitza Stark Phenotypes for gene: THRB were changed from to Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, autosomal dominant, MIM# 188570
Intellectual disability syndromic and non-syndromic v0.2297 THRB Zornitza Stark Publications for gene: THRB were set to
Intellectual disability syndromic and non-syndromic v0.2296 THRB Zornitza Stark Mode of inheritance for gene: THRB was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2295 THRB Zornitza Stark Classified gene: THRB as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2295 THRB Zornitza Stark Gene: thrb has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2294 THRB Zornitza Stark Classified gene: THRB as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2294 THRB Zornitza Stark Gene: thrb has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2293 THRB Zornitza Stark reviewed gene: THRB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid hormone resistance, autosomal recessive, MIM# 274300, Thyroid hormone resistance, autosomal dominant, MIM# 188570; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2293 TGFB1 Zornitza Stark Classified gene: TGFB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2293 TGFB1 Zornitza Stark Gene: tgfb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2292 TGFB1 Zornitza Stark gene: TGFB1 was added
gene: TGFB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TGFB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TGFB1 were set to 29483653
Phenotypes for gene: TGFB1 were set to Inflammatory bowel disease, immunodeficiency, and encephalopathy, MIM# 618213
Review for gene: TGFB1 was set to AMBER
Added comment: Three individuals from two unrelated families reported. DD/ID and seizures in addition to IBD/immunodeficiency.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2291 TERT Zornitza Stark reviewed gene: TERT: Rating: GREEN; Mode of pathogenicity: None; Publications: 18042801, 17785587; Phenotypes: Hoyeraal-Hreidarsson syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2291 TELO2 Zornitza Stark Marked gene: TELO2 as ready
Intellectual disability syndromic and non-syndromic v0.2291 TELO2 Zornitza Stark Gene: telo2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2291 TELO2 Zornitza Stark Classified gene: TELO2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2291 TELO2 Zornitza Stark Gene: telo2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2290 TELO2 Zornitza Stark gene: TELO2 was added
gene: TELO2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TELO2 were set to 27132593; 28944240
Phenotypes for gene: TELO2 were set to You-Hoover-Fong syndrome, MIM#616954; Syndromic intellectual disability
Review for gene: TELO2 was set to GREEN
Added comment: Five unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2289 TECR Zornitza Stark Marked gene: TECR as ready
Intellectual disability syndromic and non-syndromic v0.2289 TECR Zornitza Stark Gene: tecr has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2289 TECR Zornitza Stark Phenotypes for gene: TECR were changed from to Mental retardation, autosomal recessive, MIM#614020
Intellectual disability syndromic and non-syndromic v0.2288 TECR Zornitza Stark Publications for gene: TECR were set to
Intellectual disability syndromic and non-syndromic v0.2287 TECR Zornitza Stark Mode of inheritance for gene: TECR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2286 TECR Zornitza Stark Classified gene: TECR as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2286 TECR Zornitza Stark Gene: tecr has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2285 TECR Zornitza Stark reviewed gene: TECR: Rating: RED; Mode of pathogenicity: None; Publications: 21212097; Phenotypes: Mental retardation, autosomal recessive, MIM#614020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2285 TBC1D7 Zornitza Stark Marked gene: TBC1D7 as ready
Intellectual disability syndromic and non-syndromic v0.2285 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2285 TBC1D7 Zornitza Stark Phenotypes for gene: TBC1D7 were changed from to Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000
Intellectual disability syndromic and non-syndromic v0.2284 TBC1D7 Zornitza Stark Publications for gene: TBC1D7 were set to
Intellectual disability syndromic and non-syndromic v0.2283 TBC1D7 Zornitza Stark Mode of inheritance for gene: TBC1D7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2282 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2282 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2281 TBC1D7 Zornitza Stark reviewed gene: TBC1D7: Rating: AMBER; Mode of pathogenicity: None; Publications: 24515783, 23687350; Phenotypes: Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2281 TASP1 Zornitza Stark changed review comment from: Four unrelated families reported; two with founder mutation. Protein interacts with KMT2A and KMT2D. Another infant with a de novo missense variant reported in a single infant with multiple congenital abnormalities, insufficient evidence for mono allelic disease at present.
Sources: Literature; to: Four unrelated families reported; two with founder mutation. Protein interacts with KMT2A and KMT2D. Another de novo missense variant reported in a single infant with multiple congenital abnormalities, insufficient evidence for mono allelic disease at present.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2281 TAF2 Zornitza Stark Marked gene: TAF2 as ready
Intellectual disability syndromic and non-syndromic v0.2281 TAF2 Zornitza Stark Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2281 TAF2 Zornitza Stark Phenotypes for gene: TAF2 were changed from to Mental retardation, autosomal recessive 40, MIM# 615599
Intellectual disability syndromic and non-syndromic v0.2280 TAF2 Zornitza Stark Publications for gene: TAF2 were set to
Intellectual disability syndromic and non-syndromic v0.2279 TAF2 Zornitza Stark Mode of inheritance for gene: TAF2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2278 TAF2 Zornitza Stark Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2278 TAF2 Zornitza Stark Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2277 TAF2 Zornitza Stark reviewed gene: TAF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21937992, 22633631, 26350204; Phenotypes: Mental retardation, autosomal recessive 40, MIM# 615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2277 TAF13 Zornitza Stark Marked gene: TAF13 as ready
Intellectual disability syndromic and non-syndromic v0.2277 TAF13 Zornitza Stark Gene: taf13 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2277 TAF13 Zornitza Stark Publications for gene: TAF13 were set to
Intellectual disability syndromic and non-syndromic v0.2276 TAF13 Zornitza Stark Phenotypes for gene: TAF13 were changed from to Mental retardation, autosomal recessive 60, MIM# 617432
Intellectual disability syndromic and non-syndromic v0.2275 TAF13 Zornitza Stark Mode of inheritance for gene: TAF13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2274 TAF13 Zornitza Stark Classified gene: TAF13 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2274 TAF13 Zornitza Stark Gene: taf13 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2273 TAF13 Zornitza Stark reviewed gene: TAF13: Rating: AMBER; Mode of pathogenicity: None; Publications: 28257693; Phenotypes: Mental retardation, autosomal recessive 60, MIM# 617432; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2273 SYT14 Zornitza Stark Phenotypes for gene: SYT14 were changed from Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229 to Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229
Intellectual disability syndromic and non-syndromic v0.2272 SYT14 Zornitza Stark Marked gene: SYT14 as ready
Intellectual disability syndromic and non-syndromic v0.2272 SYT14 Zornitza Stark Gene: syt14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2272 SYT14 Zornitza Stark Phenotypes for gene: SYT14 were changed from to Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229
Intellectual disability syndromic and non-syndromic v0.2271 SYT14 Zornitza Stark Publications for gene: SYT14 were set to
Intellectual disability syndromic and non-syndromic v0.2270 SYT14 Zornitza Stark Mode of inheritance for gene: SYT14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2269 SYT14 Zornitza Stark Classified gene: SYT14 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2269 SYT14 Zornitza Stark Gene: syt14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2268 SYT14 Zornitza Stark reviewed gene: SYT14: Rating: RED; Mode of pathogenicity: None; Publications: 21835308; Phenotypes: Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2268 SUZ12 Zornitza Stark Phenotypes for gene: SUZ12 were changed from no OMIM number yet. to Imagawa-Matsumoto syndrome, MIM# 618786; Intellectual disability; Overgrowth
Intellectual disability syndromic and non-syndromic v0.2267 SUZ12 Zornitza Stark reviewed gene: SUZ12: Rating: GREEN; Mode of pathogenicity: None; Publications: 31736240, 30019515, 28229514; Phenotypes: Imagawa-Matsumoto syndrome, MIM# 618786, Intellectual disability, Overgrowth; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2267 SUFU Zornitza Stark Marked gene: SUFU as ready
Intellectual disability syndromic and non-syndromic v0.2267 SUFU Zornitza Stark Gene: sufu has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2267 SUFU Zornitza Stark Classified gene: SUFU as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2267 SUFU Zornitza Stark Gene: sufu has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2266 SUFU Zornitza Stark gene: SUFU was added
gene: SUFU was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SUFU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUFU were set to 28965847
Phenotypes for gene: SUFU were set to Joubert syndrome 32, MIM#617757
Review for gene: SUFU was set to AMBER
Added comment: Two unrelated families described with what are postulated to be hypomorphic bi-allelic variants in this gene and Joubert syndrome. Note gene also causes dominant Basal Cell Nevus Syndrome.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2265 STX11 Zornitza Stark Marked gene: STX11 as ready
Intellectual disability syndromic and non-syndromic v0.2265 STX11 Zornitza Stark Gene: stx11 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2265 STX11 Zornitza Stark Phenotypes for gene: STX11 were changed from to Hemophagocytic lymphohistiocytosis, familial, 4, MIM# 603552
Intellectual disability syndromic and non-syndromic v0.2264 STX11 Zornitza Stark Mode of inheritance for gene: STX11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2263 STX11 Zornitza Stark Classified gene: STX11 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2263 STX11 Zornitza Stark Gene: stx11 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2262 STX11 Zornitza Stark reviewed gene: STX11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemophagocytic lymphohistiocytosis, familial, 4, MIM# 603552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2262 STT3A Zornitza Stark edited their review of gene: STT3A: Changed rating: GREEN; Changed publications: 23842455, 30701557, 28424003; Changed phenotypes: Congenital disorder of glycosylation, type Iw, OMIM #615596; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2262 STRADA Zornitza Stark Marked gene: STRADA as ready
Intellectual disability syndromic and non-syndromic v0.2262 STRADA Zornitza Stark Gene: strada has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2262 STRADA Zornitza Stark Classified gene: STRADA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2262 STRADA Zornitza Stark Gene: strada has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2261 STRADA Zornitza Stark gene: STRADA was added
gene: STRADA was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: STRADA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STRADA were set to 17522105; 27170158; 28688840
Phenotypes for gene: STRADA were set to Polyhydramnios, megalencephaly, and symptomatic epilepsy, MIM# 611087
Review for gene: STRADA was set to GREEN
Added comment: Seven distantly related Menonite children plus four other unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2260 SRPX2 Zornitza Stark Marked gene: SRPX2 as ready
Intellectual disability syndromic and non-syndromic v0.2260 SRPX2 Zornitza Stark Gene: srpx2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2260 SRPX2 Zornitza Stark Phenotypes for gene: SRPX2 were changed from to Rolandic epilepsy, mental retardation, and speech dyspraxia, MIM# 300643
Intellectual disability syndromic and non-syndromic v0.2259 SRPX2 Zornitza Stark Publications for gene: SRPX2 were set to
Intellectual disability syndromic and non-syndromic v0.2258 SRPX2 Zornitza Stark Mode of inheritance for gene: SRPX2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2257 SRPX2 Zornitza Stark Classified gene: SRPX2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2257 SRPX2 Zornitza Stark Gene: srpx2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2256 SRPX2 Zornitza Stark reviewed gene: SRPX2: Rating: RED; Mode of pathogenicity: None; Publications: 16497722, 23933820, 23871722; Phenotypes: Rolandic epilepsy, mental retardation, and speech dyspraxia, MIM# 300643; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2256 SPRTN Zornitza Stark Marked gene: SPRTN as ready
Intellectual disability syndromic and non-syndromic v0.2256 SPRTN Zornitza Stark Gene: sprtn has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2256 SPRTN Zornitza Stark Phenotypes for gene: SPRTN were changed from to Ruijs-Aalfs syndrome, MIM# 616200
Intellectual disability syndromic and non-syndromic v0.2255 SPRTN Zornitza Stark Publications for gene: SPRTN were set to
Intellectual disability syndromic and non-syndromic v0.2254 SPRTN Zornitza Stark Mode of inheritance for gene: SPRTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2253 SPRTN Zornitza Stark Classified gene: SPRTN as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2253 SPRTN Zornitza Stark Gene: sprtn has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2252 SPRTN Zornitza Stark reviewed gene: SPRTN: Rating: RED; Mode of pathogenicity: None; Publications: 25261934; Phenotypes: Ruijs-Aalfs syndrome, MIM# 616200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2252 KMT2A Zornitza Stark Marked gene: KMT2A as ready
Intellectual disability syndromic and non-syndromic v0.2252 KMT2A Zornitza Stark Gene: kmt2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2252 KMT2A Zornitza Stark Phenotypes for gene: KMT2A were changed from to Wiedemann-Steiner syndrome, MIM# 605130 AD
Intellectual disability syndromic and non-syndromic v0.2251 KMT2A Zornitza Stark Mode of inheritance for gene: KMT2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2250 KMT2A Zornitza Stark reviewed gene: KMT2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wiedemann-Steiner syndrome, MIM# 605130 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2250 CEP135 Zornitza Stark Marked gene: CEP135 as ready
Intellectual disability syndromic and non-syndromic v0.2250 CEP135 Zornitza Stark Gene: cep135 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2250 CEP135 Zornitza Stark Phenotypes for gene: CEP135 were changed from Microcephalic primordial dwarfism; Microcephaly 8, primary, autosomal recessive, 614673 to Microcephalic primordial dwarfism; Microcephaly 8, primary, autosomal recessive, 614673
Intellectual disability syndromic and non-syndromic v0.2250 CEP135 Zornitza Stark Phenotypes for gene: CEP135 were changed from to Microcephalic primordial dwarfism; Microcephaly 8, primary, autosomal recessive, 614673
Intellectual disability syndromic and non-syndromic v0.2249 CEP135 Zornitza Stark Publications for gene: CEP135 were set to
Intellectual disability syndromic and non-syndromic v0.2248 CEP135 Zornitza Stark Mode of inheritance for gene: CEP135 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2247 CEP135 Zornitza Stark reviewed gene: CEP135: Rating: GREEN; Mode of pathogenicity: None; Publications: 30214071, 22521416; Phenotypes: Microcephalic primordial dwarfism, Microcephaly 8, primary, autosomal recessive, 614673; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2247 CDK13 Zornitza Stark Phenotypes for gene: CDK13 were changed from Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, 617360 to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, 617360
Intellectual disability syndromic and non-syndromic v0.2247 CDK13 Zornitza Stark Marked gene: CDK13 as ready
Intellectual disability syndromic and non-syndromic v0.2247 CDK13 Zornitza Stark Gene: cdk13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2247 CDK13 Zornitza Stark Phenotypes for gene: CDK13 were changed from to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, 617360
Intellectual disability syndromic and non-syndromic v0.2246 CDK13 Zornitza Stark Publications for gene: CDK13 were set to
Intellectual disability syndromic and non-syndromic v0.2245 CDK13 Zornitza Stark Mode of inheritance for gene: CDK13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2244 CDK13 Zornitza Stark reviewed gene: CDK13: Rating: GREEN; Mode of pathogenicity: None; Publications: 29021403, 29393965, 30904094; Phenotypes: Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, 617360; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2244 SPG7 Zornitza Stark Classified gene: SPG7 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2244 SPG7 Zornitza Stark Gene: spg7 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2243 SPG7 Zornitza Stark reviewed gene: SPG7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 7, autosomal recessive, MIM# 607259; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2243 SPAST Zornitza Stark Marked gene: SPAST as ready
Intellectual disability syndromic and non-syndromic v0.2243 SPAST Zornitza Stark Gene: spast has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2243 SPAST Zornitza Stark Phenotypes for gene: SPAST were changed from to Spastic paraplegia 4, autosomal dominant, MIM# 182601
Intellectual disability syndromic and non-syndromic v0.2242 SPAST Zornitza Stark Mode of inheritance for gene: SPAST was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2241 SPAST Zornitza Stark Classified gene: SPAST as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2241 SPAST Zornitza Stark Gene: spast has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2240 SPAST Zornitza Stark reviewed gene: SPAST: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 4, autosomal dominant, MIM# 182601; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2240 SOS2 Zornitza Stark Marked gene: SOS2 as ready
Intellectual disability syndromic and non-syndromic v0.2240 SOS2 Zornitza Stark Gene: sos2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2240 SOS2 Zornitza Stark Classified gene: SOS2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2240 SOS2 Zornitza Stark Gene: sos2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2239 SOS2 Zornitza Stark gene: SOS2 was added
gene: SOS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SOS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SOS2 were set to Noonan syndrome 9, MIM# 616559
Review for gene: SOS2 was set to GREEN
Added comment: Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2238 RASA1 Zornitza Stark reviewed gene: RASA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Capillary malformation-arteriovenous malformation 1, MIM# 608354; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2238 RASA1 Sebastian Lunke Marked gene: RASA1 as ready
Intellectual disability syndromic and non-syndromic v0.2238 RASA1 Sebastian Lunke Gene: rasa1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2238 RASA1 Sebastian Lunke gene: RASA1 was added
gene: RASA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: RASA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for gene: RASA1 was set to RED
Added comment: GEL review red in 2018, no evidence for link with ID since
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2237 RAX Sebastian Lunke gene: RAX was added
gene: RAX was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: RAX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAX were set to 30762128; 24033328
Phenotypes for gene: RAX were set to MICROPHTHALMIA, ISOLATED 3; MCOP3
Review for gene: RAX was set to RED
Added comment: Only three cases described with intellectual disability in addition to microphthalmia, no new descriptions of ID association since 2014. Not clear if the cases are from the same or different families. Link with ID seems tenuous at best.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2236 ZFHX3 Zornitza Stark Classified gene: ZFHX3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2236 ZFHX3 Zornitza Stark Gene: zfhx3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2235 SOBP Zornitza Stark Marked gene: SOBP as ready
Intellectual disability syndromic and non-syndromic v0.2235 SOBP Zornitza Stark Gene: sobp has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2235 SOBP Zornitza Stark Phenotypes for gene: SOBP were changed from Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671 to Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671
Intellectual disability syndromic and non-syndromic v0.2234 SOBP Zornitza Stark Phenotypes for gene: SOBP were changed from to Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671
Intellectual disability syndromic and non-syndromic v0.2234 SOBP Zornitza Stark Publications for gene: SOBP were set to 21035105
Intellectual disability syndromic and non-syndromic v0.2233 SOBP Zornitza Stark Publications for gene: SOBP were set to
Intellectual disability syndromic and non-syndromic v0.2233 SOBP Zornitza Stark Mode of inheritance for gene: SOBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2232 SOBP Zornitza Stark Classified gene: SOBP as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2232 SOBP Zornitza Stark Gene: sobp has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2231 SOBP Zornitza Stark reviewed gene: SOBP: Rating: RED; Mode of pathogenicity: None; Publications: 21035105; Phenotypes: Mental retardation, anterior maxillary protrusion, and strabismus, MIM# 613671; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2231 SNORD118 Zornitza Stark Classified gene: SNORD118 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2231 SNORD118 Zornitza Stark Gene: snord118 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2230 SNORD118 Zornitza Stark reviewed gene: SNORD118: Rating: AMBER; Mode of pathogenicity: None; Publications: 27571260; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts, MIM# 614561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2230 SNIP1 Zornitza Stark Marked gene: SNIP1 as ready
Intellectual disability syndromic and non-syndromic v0.2230 SNIP1 Zornitza Stark Gene: snip1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2230 SNIP1 Zornitza Stark Phenotypes for gene: SNIP1 were changed from Psychomotor retardation, epilepsy, and craniofacial dysmorphism, MIM# 614501 to Psychomotor retardation, epilepsy, and craniofacial dysmorphism, MIM# 614501
Intellectual disability syndromic and non-syndromic v0.2229 SNIP1 Zornitza Stark Phenotypes for gene: SNIP1 were changed from to Psychomotor retardation, epilepsy, and craniofacial dysmorphism, MIM# 614501
Intellectual disability syndromic and non-syndromic v0.2229 SNIP1 Zornitza Stark Publications for gene: SNIP1 were set to 22279524
Intellectual disability syndromic and non-syndromic v0.2228 SNIP1 Zornitza Stark Publications for gene: SNIP1 were set to
Intellectual disability syndromic and non-syndromic v0.2228 SNIP1 Zornitza Stark Mode of inheritance for gene: SNIP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2227 SNIP1 Zornitza Stark Classified gene: SNIP1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2227 SNIP1 Zornitza Stark Gene: snip1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2226 SNIP1 Zornitza Stark reviewed gene: SNIP1: Rating: RED; Mode of pathogenicity: None; Publications: 22279524; Phenotypes: Psychomotor retardation, epilepsy, and craniofacial dysmorphism, MIM# 614501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2226 SMG9 Zornitza Stark Marked gene: SMG9 as ready
Intellectual disability syndromic and non-syndromic v0.2226 SMG9 Zornitza Stark Gene: smg9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2226 SMG9 Zornitza Stark Classified gene: SMG9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2226 SMG9 Zornitza Stark Gene: smg9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2225 SMG9 Zornitza Stark gene: SMG9 was added
gene: SMG9 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SMG9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMG9 were set to 27018474; 31390136
Phenotypes for gene: SMG9 were set to Heart and brain malformation syndrome, MIM# 616920
Review for gene: SMG9 was set to GREEN
Added comment: Three unrelated families reported, severe congenital malformation syndrome, ID is part of the phenotype in survivors.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2224 SMARCD2 Zornitza Stark Marked gene: SMARCD2 as ready
Intellectual disability syndromic and non-syndromic v0.2224 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2224 SMARCD2 Zornitza Stark Classified gene: SMARCD2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2224 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2223 SMARCD2 Zornitza Stark gene: SMARCD2 was added
gene: SMARCD2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCD2 were set to 26350204; 28369036
Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2, 617475 (includes global developmental delay in some patients)
Review for gene: SMARCD2 was set to AMBER
Added comment: Candidate ID gene in PMID:26350204 and developmental delay seen in 2 patients with SGD2 PMID:28369036.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2222 PIGA Zornitza Stark Marked gene: PIGA as ready
Intellectual disability syndromic and non-syndromic v0.2222 PIGA Zornitza Stark Gene: piga has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2222 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868
Intellectual disability syndromic and non-syndromic v0.2221 PIGA Zornitza Stark Publications for gene: PIGA were set to
Intellectual disability syndromic and non-syndromic v0.2220 PIGA Zornitza Stark Mode of inheritance for gene: PIGA was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2219 PIGA Zornitza Stark reviewed gene: PIGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 24706016, 24259184, 29159939; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM#300868; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2219 WDR81 Zornitza Stark reviewed gene: WDR81: Rating: GREEN; Mode of pathogenicity: None; Publications: 21885617, 28556411, 28969387; Phenotypes: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185, Hydrocephalus, congenital, 3, with brain anomalies, 617967; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2219 SLC9A9 Zornitza Stark Marked gene: SLC9A9 as ready
Intellectual disability syndromic and non-syndromic v0.2219 SLC9A9 Zornitza Stark Gene: slc9a9 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2219 SLC9A9 Zornitza Stark Phenotypes for gene: SLC9A9 were changed from to {?Autism susceptibility 16}, MIM# 613410
Intellectual disability syndromic and non-syndromic v0.2218 SLC9A9 Zornitza Stark Publications for gene: SLC9A9 were set to
Intellectual disability syndromic and non-syndromic v0.2217 SLC9A9 Zornitza Stark Classified gene: SLC9A9 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2217 SLC9A9 Zornitza Stark Gene: slc9a9 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2216 SLC9A9 Zornitza Stark reviewed gene: SLC9A9: Rating: RED; Mode of pathogenicity: None; Publications: 18621663, 31134136, 27123481, 26755066; Phenotypes: {?Autism susceptibility 16}, MIM# 613410; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2216 SLC7A7 Zornitza Stark Marked gene: SLC7A7 as ready
Intellectual disability syndromic and non-syndromic v0.2216 SLC7A7 Zornitza Stark Gene: slc7a7 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2216 SLC7A7 Zornitza Stark Phenotypes for gene: SLC7A7 were changed from to Lysinuric protein intolerance, MIM# 222700
Intellectual disability syndromic and non-syndromic v0.2215 SLC7A7 Zornitza Stark Mode of inheritance for gene: SLC7A7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2214 SLC7A7 Zornitza Stark Classified gene: SLC7A7 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2214 SLC7A7 Zornitza Stark Gene: slc7a7 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2213 SLC7A7 Zornitza Stark reviewed gene: SLC7A7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lysinuric protein intolerance, MIM# 222700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2213 SLC6A4 Zornitza Stark Marked gene: SLC6A4 as ready
Intellectual disability syndromic and non-syndromic v0.2213 SLC6A4 Zornitza Stark Gene: slc6a4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2213 SLC6A4 Zornitza Stark Phenotypes for gene: SLC6A4 were changed from {Obsessive-compulsive disorder}, MIM# 164230; depression; alcohol dependence to {Obsessive-compulsive disorder}, MIM# 164230; depression; alcohol dependence
Intellectual disability syndromic and non-syndromic v0.2212 SLC6A4 Zornitza Stark Phenotypes for gene: SLC6A4 were changed from to {Obsessive-compulsive disorder}, MIM# 164230; depression; alcohol dependence
Intellectual disability syndromic and non-syndromic v0.2212 SLC6A4 Zornitza Stark Mode of inheritance for gene: SLC6A4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2211 SLC6A4 Zornitza Stark Publications for gene: SLC6A4 were set to
Intellectual disability syndromic and non-syndromic v0.2211 SLC6A4 Zornitza Stark Mode of inheritance for gene: SLC6A4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2210 SLC6A4 Zornitza Stark Classified gene: SLC6A4 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2210 SLC6A4 Zornitza Stark Gene: slc6a4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2209 SLC6A4 Zornitza Stark reviewed gene: SLC6A4: Rating: RED; Mode of pathogenicity: None; Publications: 31629822; Phenotypes: {Obsessive-compulsive disorder}, MIM# 164230, depression, alcohol dependence; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2209 PNKP Zornitza Stark Marked gene: PNKP as ready
Intellectual disability syndromic and non-syndromic v0.2209 PNKP Zornitza Stark Added comment: Comment when marking as ready: Note 17-bp duplication (1250_1266dup) in exon 14 identified in multiple individuals.
Intellectual disability syndromic and non-syndromic v0.2209 PNKP Zornitza Stark Gene: pnkp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2209 PNKP Zornitza Stark Phenotypes for gene: PNKP were changed from to Microcephaly, seizures, and developmental delay, MIM#613402
Intellectual disability syndromic and non-syndromic v0.2208 PNKP Zornitza Stark Publications for gene: PNKP were set to
Intellectual disability syndromic and non-syndromic v0.2207 PNKP Zornitza Stark Mode of inheritance for gene: PNKP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2206 PNKP Zornitza Stark reviewed gene: PNKP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23224214, 20118933; Phenotypes: Microcephaly, seizures, and developmental delay, MIM#613402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2206 SLC25A24 Zornitza Stark Marked gene: SLC25A24 as ready
Intellectual disability syndromic and non-syndromic v0.2206 SLC25A24 Zornitza Stark Gene: slc25a24 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2206 SLC25A24 Zornitza Stark Phenotypes for gene: SLC25A24 were changed from to Fontaine progeroid syndrome, MIM#612289
Intellectual disability syndromic and non-syndromic v0.2205 SLC25A24 Zornitza Stark Mode of inheritance for gene: SLC25A24 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2204 SLC25A24 Zornitza Stark Classified gene: SLC25A24 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2204 SLC25A24 Zornitza Stark Gene: slc25a24 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2203 SLC25A24 Zornitza Stark reviewed gene: SLC25A24: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fontaine progeroid syndrome, MIM#612289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2203 SLC25A19 Zornitza Stark Classified gene: SLC25A19 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2203 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2202 SLC25A19 Zornitza Stark changed review comment from: Bi-alllelic variants in this gene have been associated with a spectrum of phenotypes, ranging from a severe neonatal disorder in the Amish, with ID as part of the phenotype through to a neuropathy.; to: Bi-alllelic variants in this gene have been associated with a spectrum of phenotypes, ranging from a severe neonatal disorder in the Amish, with ID as part of the phenotype (founder effect) through to a neuropathy/disorder of episodic encephalopathy.
Intellectual disability syndromic and non-syndromic v0.2202 SLC25A19 Zornitza Stark edited their review of gene: SLC25A19: Changed rating: RED
Intellectual disability syndromic and non-syndromic v0.2202 SLC1A2 Zornitza Stark Marked gene: SLC1A2 as ready
Intellectual disability syndromic and non-syndromic v0.2202 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2202 SLC1A2 Zornitza Stark Classified gene: SLC1A2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2202 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2201 SLC1A2 Zornitza Stark gene: SLC1A2 was added
gene: SLC1A2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SLC1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A2 were set to 27476654; 28777935
Phenotypes for gene: SLC1A2 were set to Epileptic encephalopathy, early infantile, 41, MIM#617105; Intellectual disability
Review for gene: SLC1A2 was set to GREEN
gene: SLC1A2 was marked as current diagnostic
Added comment: Four unrelated individuals reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2200 SHROOM4 Zornitza Stark Marked gene: SHROOM4 as ready
Intellectual disability syndromic and non-syndromic v0.2200 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2200 SHROOM4 Zornitza Stark Phenotypes for gene: SHROOM4 were changed from to Stocco dos Santos X-linked mental retardation syndrome, 300434; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.2199 SHROOM4 Zornitza Stark Publications for gene: SHROOM4 were set to
Intellectual disability syndromic and non-syndromic v0.2198 SHROOM4 Zornitza Stark Mode of inheritance for gene: SHROOM4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2197 SHROOM4 Zornitza Stark Classified gene: SHROOM4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2197 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2196 SHROOM4 Zornitza Stark reviewed gene: SHROOM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 16249884, 26740508; Phenotypes: Stocco dos Santos X-linked mental retardation syndrome, 300434, Intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2196 CHD2 Zornitza Stark Marked gene: CHD2 as ready
Intellectual disability syndromic and non-syndromic v0.2196 CHD2 Zornitza Stark Gene: chd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2196 CHD2 Zornitza Stark Phenotypes for gene: CHD2 were changed from to Epileptic encephalopathy, childhood-onset (MIM # 615369)
Intellectual disability syndromic and non-syndromic v0.2195 CHD2 Zornitza Stark Mode of inheritance for gene: CHD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2194 INTS1 Zornitza Stark Marked gene: INTS1 as ready
Intellectual disability syndromic and non-syndromic v0.2194 INTS1 Zornitza Stark Gene: ints1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2194 INTS1 Zornitza Stark Phenotypes for gene: INTS1 were changed from to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, MIM# 618571
Intellectual disability syndromic and non-syndromic v0.2193 INTS1 Zornitza Stark Publications for gene: INTS1 were set to
Intellectual disability syndromic and non-syndromic v0.2192 INTS1 Zornitza Stark Mode of inheritance for gene: INTS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2191 INTS1 Chern Lim reviewed gene: INTS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28542170, 30622326, 31428919; Phenotypes: Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, MIM# 618571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2191 SEMA3E Zornitza Stark Classified gene: SEMA3E as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2191 SEMA3E Zornitza Stark Gene: sema3e has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2190 SACS Zornitza Stark Marked gene: SACS as ready
Intellectual disability syndromic and non-syndromic v0.2190 SACS Zornitza Stark Gene: sacs has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2190 SACS Zornitza Stark Phenotypes for gene: SACS were changed from to Spastic ataxia, Charlevoix-Saguenay type, MIM# 270550
Intellectual disability syndromic and non-syndromic v0.2189 SACS Zornitza Stark Publications for gene: SACS were set to
Intellectual disability syndromic and non-syndromic v0.2188 SACS Zornitza Stark Mode of inheritance for gene: SACS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2187 SACS Zornitza Stark Classified gene: SACS as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2187 SACS Zornitza Stark Gene: sacs has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2186 SACS Zornitza Stark reviewed gene: SACS: Rating: AMBER; Mode of pathogenicity: None; Publications: 28843771, 20876471, 28658676, 27871429; Phenotypes: Spastic ataxia, Charlevoix-Saguenay type, MIM# 270550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2186 SOX3 Zornitza Stark Tag SV/CNV tag was added to gene: SOX3.
Intellectual disability syndromic and non-syndromic v0.2186 SOX3 Zornitza Stark Marked gene: SOX3 as ready
Intellectual disability syndromic and non-syndromic v0.2186 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2186 SOX3 Zornitza Stark Phenotypes for gene: SOX3 were changed from to Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123; Panhypopituitarism, X-linked, MIM#312000
Intellectual disability syndromic and non-syndromic v0.2185 SOX3 Zornitza Stark Publications for gene: SOX3 were set to
Intellectual disability syndromic and non-syndromic v0.2184 SOX3 Zornitza Stark Mode of pathogenicity for gene: SOX3 was changed from to Other
Intellectual disability syndromic and non-syndromic v0.2183 SOX3 Zornitza Stark Mode of inheritance for gene: SOX3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2182 SOX3 Zornitza Stark Classified gene: SOX3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2182 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2181 SOX3 Zornitza Stark edited their review of gene: SOX3: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.2181 SOX3 Zornitza Stark reviewed gene: SOX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked, with isolated growth hormone deficiency, MIM# 300123; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2181 PUF60 Zornitza Stark Marked gene: PUF60 as ready
Intellectual disability syndromic and non-syndromic v0.2181 PUF60 Zornitza Stark Gene: puf60 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2181 PUF60 Zornitza Stark Phenotypes for gene: PUF60 were changed from to Verheij syndrome, MIM# 615583
Intellectual disability syndromic and non-syndromic v0.2180 PUF60 Zornitza Stark Publications for gene: PUF60 were set to
Intellectual disability syndromic and non-syndromic v0.2179 PUF60 Zornitza Stark Mode of inheritance for gene: PUF60 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2178 PUF60 Zornitza Stark reviewed gene: PUF60: Rating: GREEN; Mode of pathogenicity: None; Publications: 28327570; Phenotypes: Verheij syndrome, MIM# 615583; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2178 SOX3 Chern Lim reviewed gene: SOX3: Rating: AMBER; Mode of pathogenicity: Other; Publications: 29175558, 30125608, 12428212, 15800844; Phenotypes: Mental retardation, X-linked, with isolated growth hormone deficiency, MIM#300123, Panhypopituitarism, X-linked, MIM#312000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2178 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.2178 PTRHD1 Zornitza Stark Marked gene: PTRHD1 as ready
Intellectual disability syndromic and non-syndromic v0.2178 PTRHD1 Zornitza Stark Gene: ptrhd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2178 PTRHD1 Zornitza Stark Classified gene: PTRHD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2178 PTRHD1 Zornitza Stark Gene: ptrhd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2177 PTRHD1 Zornitza Stark gene: PTRHD1 was added
gene: PTRHD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PTRHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTRHD1 were set to 30398675; 27134041; 27753167; 29143421
Phenotypes for gene: PTRHD1 were set to Parkinsonism; Intellectual disability
Review for gene: PTRHD1 was set to GREEN
Added comment: Three unrelated families reported: two with homozygous missense variants; and one with truncating variant. Affected individuals have juvenile-onset parkinsonism and ID.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2176 PTRH2 Zornitza Stark Marked gene: PTRH2 as ready
Intellectual disability syndromic and non-syndromic v0.2176 PTRH2 Zornitza Stark Gene: ptrh2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2176 PTRH2 Zornitza Stark Classified gene: PTRH2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2176 PTRH2 Zornitza Stark Gene: ptrh2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2175 PTRH2 Zornitza Stark gene: PTRH2 was added
gene: PTRH2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PTRH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTRH2 were set to 25574476; 28175314; 28328138; 25558065; 27129381
Phenotypes for gene: PTRH2 were set to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, MIM# 616263
Review for gene: PTRH2 was set to AMBER
Added comment: A spectrum of features associated with bi-allelic variants in this gene; however, ID only reported as a feature in two families.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2174 PSAT1 Zornitza Stark Marked gene: PSAT1 as ready
Intellectual disability syndromic and non-syndromic v0.2174 PSAT1 Zornitza Stark Gene: psat1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2174 PSAT1 Zornitza Stark Phenotypes for gene: PSAT1 were changed from to Phosphoserine aminotransferase deficiency, MIM# 610992; Neu-Laxova syndrome 2, MIM# 616038
Intellectual disability syndromic and non-syndromic v0.2173 PSAT1 Zornitza Stark Publications for gene: PSAT1 were set to
Intellectual disability syndromic and non-syndromic v0.2172 PSAT1 Zornitza Stark Mode of inheritance for gene: PSAT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2172 PSAT1 Zornitza Stark Mode of inheritance for gene: PSAT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2171 PSAT1 Zornitza Stark Classified gene: PSAT1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2171 PSAT1 Zornitza Stark Gene: psat1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2170 PSAT1 Zornitza Stark reviewed gene: PSAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26960553, 17436247, 25152457; Phenotypes: Phosphoserine aminotransferase deficiency, MIM# 610992, Neu-Laxova syndrome 2, MIM# 616038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2170 PRRT2 Zornitza Stark Phenotypes for gene: PRRT2 were changed from Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066; Episodic kinesigenic dyskinesia 1, MIM# 128200; Seizures, benign familial infantile, 2, MIM# 605751 to Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066; Episodic kinesigenic dyskinesia 1, MIM# 128200; Seizures, benign familial infantile, 2, MIM# 605751; intellectual disability, autosomal recessive
Intellectual disability syndromic and non-syndromic v0.2169 PRRT2 Zornitza Stark Publications for gene: PRRT2 were set to
Intellectual disability syndromic and non-syndromic v0.2168 PRRT2 Zornitza Stark Mode of inheritance for gene: PRRT2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2167 PRRT2 Zornitza Stark Classified gene: PRRT2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2167 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2166 PRRT2 Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: ID is not part of the phenotype for the mono allelic conditions; two families described with bi-allelic variants and more severe neurological phenotype, including ID.
Intellectual disability syndromic and non-syndromic v0.2166 PRRT2 Zornitza Stark edited their review of gene: PRRT2: Changed phenotypes: Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066, Episodic kinesigenic dyskinesia 1, MIM# 128200, Seizures, benign familial infantile, 2, MIM# 605751, intellectual disability, autosomal recessive
Intellectual disability syndromic and non-syndromic v0.2166 PRRT2 Zornitza Stark edited their review of gene: PRRT2: Changed rating: AMBER; Changed publications: 23352743, 25595153, 23398397; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2166 PRRT2 Zornitza Stark Marked gene: PRRT2 as ready
Intellectual disability syndromic and non-syndromic v0.2166 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2166 PRRT2 Zornitza Stark Phenotypes for gene: PRRT2 were changed from to Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066; Episodic kinesigenic dyskinesia 1, MIM# 128200; Seizures, benign familial infantile, 2, MIM# 605751
Intellectual disability syndromic and non-syndromic v0.2165 PRRT2 Zornitza Stark Mode of inheritance for gene: PRRT2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2164 PRRT2 Zornitza Stark Classified gene: PRRT2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2164 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2163 PRRT2 Zornitza Stark reviewed gene: PRRT2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066, Episodic kinesigenic dyskinesia 1, MIM# 128200, Seizures, benign familial infantile, 2, MIM# 605751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2163 POU1F1 Zornitza Stark Marked gene: POU1F1 as ready
Intellectual disability syndromic and non-syndromic v0.2163 POU1F1 Zornitza Stark Gene: pou1f1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2163 POU1F1 Zornitza Stark Phenotypes for gene: POU1F1 were changed from to Pituitary hormone deficiency, combined, 1, MIM# 613038
Intellectual disability syndromic and non-syndromic v0.2162 POU1F1 Zornitza Stark Mode of inheritance for gene: POU1F1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2161 POU1F1 Zornitza Stark Classified gene: POU1F1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2161 POU1F1 Zornitza Stark Gene: pou1f1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2160 POU1F1 Zornitza Stark reviewed gene: POU1F1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 1, MIM# 613038; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2160 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Intellectual disability syndromic and non-syndromic v0.2160 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2160 POLR1C Zornitza Stark Classified gene: POLR1C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2160 POLR1C Zornitza Stark Gene: polr1c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2159 POLR1C Zornitza Stark gene: POLR1C was added
gene: POLR1C was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to 26151409
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, MIM# 616494
Review for gene: POLR1C was set to GREEN
Added comment: 8 unrelated individuals reported, ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2158 PNP Zornitza Stark Classified gene: PNP as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2158 PNP Zornitza Stark Gene: pnp has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2157 PNP Zornitza Stark Deleted their comment
Intellectual disability syndromic and non-syndromic v0.2157 PNP Zornitza Stark edited their review of gene: PNP: Added comment: Neurological phenotype is predominantly spasticity rather than ID.; Changed rating: RED
Intellectual disability syndromic and non-syndromic v0.2157 PMPCA Zornitza Stark Marked gene: PMPCA as ready
Intellectual disability syndromic and non-syndromic v0.2157 PMPCA Zornitza Stark Gene: pmpca has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2157 PMPCA Zornitza Stark Classified gene: PMPCA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2157 PMPCA Zornitza Stark Gene: pmpca has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2156 PMPCA Zornitza Stark gene: PMPCA was added
gene: PMPCA was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PMPCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMPCA were set to 25808372; 26657514; 27148589; 30617178
Phenotypes for gene: PMPCA were set to Spinocerebellar ataxia, autosomal recessive 2, MIM# 213200
Review for gene: PMPCA was set to GREEN
Added comment: Seven families reported. Three had the same founder variant. ID observed in five of the affected families (includes the three with the same founder variant).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2155 GFER Zornitza Stark Marked gene: GFER as ready
Intellectual disability syndromic and non-syndromic v0.2155 GFER Zornitza Stark Gene: gfer has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2155 GFER Zornitza Stark Phenotypes for gene: GFER were changed from to Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay (MIM #613076)
Intellectual disability syndromic and non-syndromic v0.2154 GFER Zornitza Stark Publications for gene: GFER were set to
Intellectual disability syndromic and non-syndromic v0.2153 GFER Zornitza Stark Mode of inheritance for gene: GFER was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2152 GFER Zornitza Stark reviewed gene: GFER: Rating: GREEN; Mode of pathogenicity: None; Publications: 28155230; Phenotypes: Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay (MIM #613076); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2152 RPIA Sebastian Lunke Marked gene: RPIA as ready
Intellectual disability syndromic and non-syndromic v0.2152 RPIA Sebastian Lunke Gene: rpia has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2152 RPIA Sebastian Lunke Classified gene: RPIA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2152 RPIA Sebastian Lunke Gene: rpia has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2151 RPIA Sebastian Lunke gene: RPIA was added
gene: RPIA was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: RPIA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPIA were set to 14988808; 10589548; 20499043; 28801340; 30088433
Phenotypes for gene: RPIA were set to Ribose 5-phosphate isomerase deficiency, MIM 608611
Review for gene: RPIA was set to GREEN
gene: RPIA was marked as current diagnostic
Added comment: From GEL: Three patients described in total, one of these with functional data:

Patient 1 with comp het missense and frameshift as well as functional data, early developmental delay, leukoencephalopathy, seizures with onset at 4 years, with subsequent neurologic regression and peripheral neuropathy

Patient 2 with missense, delayed early development, seizures and regression at the age of 7 with MRI white matter abnormalities

Patient 3 with comp het missense and canonical splice, clinical biochem corroboration ribitol and arabitol in urine demonstrated significant elevations (>20x), neonatal onset leukoencephalopathy and developmental delay
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.2150 PLEKHG2 Zornitza Stark Marked gene: PLEKHG2 as ready
Intellectual disability syndromic and non-syndromic v0.2150 PLEKHG2 Zornitza Stark Gene: plekhg2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2150 PLEKHG2 Zornitza Stark Classified gene: PLEKHG2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2150 PLEKHG2 Zornitza Stark Gene: plekhg2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2149 PLEKHG2 Zornitza Stark gene: PLEKHG2 was added
gene: PLEKHG2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PLEKHG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEKHG2 were set to 26539891; 24001768; 26573021
Phenotypes for gene: PLEKHG2 were set to Leukodystrophy and acquired microcephaly with or without dystonia, 616763
Review for gene: PLEKHG2 was set to AMBER
Added comment: Three families reported; however, two had the same homozygous variant (founder effect).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2148 PITRM1 Zornitza Stark Marked gene: PITRM1 as ready
Intellectual disability syndromic and non-syndromic v0.2148 PITRM1 Zornitza Stark Gene: pitrm1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2148 PITRM1 Zornitza Stark Classified gene: PITRM1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2148 PITRM1 Zornitza Stark Gene: pitrm1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2147 PITRM1 Zornitza Stark gene: PITRM1 was added
gene: PITRM1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PITRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PITRM1 were set to 26697887; 29764912; 29383861
Phenotypes for gene: PITRM1 were set to Ataxia; Intellectual disability
Review for gene: PITRM1 was set to GREEN
gene: PITRM1 was marked as current diagnostic
Added comment: Three unrelated families reported with bi-allelic variants in this gene.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2146 PIK3C2A Zornitza Stark Marked gene: PIK3C2A as ready
Intellectual disability syndromic and non-syndromic v0.2146 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2146 PIK3C2A Zornitza Stark Classified gene: PIK3C2A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2146 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2145 PIK3C2A Zornitza Stark gene: PIK3C2A was added
gene: PIK3C2A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3C2A were set to 31034465
Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome, 618440
Review for gene: PIK3C2A was set to GREEN
Added comment: Three unrelated families, ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2144 MECP2 Zornitza Stark Marked gene: MECP2 as ready
Intellectual disability syndromic and non-syndromic v0.2144 MECP2 Zornitza Stark Gene: mecp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2144 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from to Encephalopathy, neonatal severe 300673 XLR; Mental retardation, X-linked, syndromic 13 300055 XLR; Rett syndrome 312750 XLD
Intellectual disability syndromic and non-syndromic v0.2143 MECP2 Zornitza Stark Publications for gene: MECP2 were set to
Intellectual disability syndromic and non-syndromic v0.2142 MECP2 Zornitza Stark Mode of inheritance for gene: MECP2 was changed from Unknown to Other
Intellectual disability syndromic and non-syndromic v0.2141 VARS Chirag Patel Classified gene: VARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2141 VARS Chirag Patel Gene: vars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2140 VARS Chirag Patel Classified gene: VARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2140 VARS Chirag Patel Gene: vars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2139 VARS Chirag Patel gene: VARS was added
gene: VARS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: VARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VARS were set to PubMed: 30755616, 30755602, 26539891, 29691655, 30275004
Phenotypes for gene: VARS were set to Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy; OMIM #617802
Review for gene: VARS was set to GREEN
Added comment: 14 families with 20 affected individuals
- homozygous missense or compound heterozygous mutations in VARS
- mutations segregated with the disorder in the families
- functional studies in some cases
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2138 WDR4 Chirag Patel changed review comment from: Galloway-Mowat syndrome 6, OMIM #618347:

1 family with 2 sibs with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 1 child with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 4 sibs with GMS and homozygous splice site mutation in the WDR4 gene. Functional studies of the variant and studies of patient cells were not performed.



Microcephaly, growth deficiency, seizures, and brain malformations; OMIM #618346:

2 unrelated patients with intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Testing found the same homozygous missense mutation in the WDR4 gene, which segregated with the disorder in both families. Studies of patient cells and modeling of the corresponding mutation in yeast showed that the mutation caused a significant reduction in m(7)G46 methylation of specific tRNAs species, particularly at higher temperatures. This was associated with a growth defect in yeast, thus offering a potential mechanism for the growth defects observed in patients with the mutation. The findings suggested that abnormal tRNA modification is a major contributor to disease pathogenesis.
Sources: Expert list; to: Galloway-Mowat syndrome 6, OMIM #618347:

1 family with 2 sibs with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 1 child with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 4 sibs with GMS and homozygous splice site mutation in the WDR4 gene. Functional studies of the variant and studies of patient cells were not performed.
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Microcephaly, growth deficiency, seizures, and brain malformations; OMIM #618346:

2 unrelated patients with intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Testing found the same homozygous missense mutation in the WDR4 gene, which segregated with the disorder in both families. Studies of patient cells and modeling of the corresponding mutation in yeast showed that the mutation caused a significant reduction in m(7)G46 methylation of specific tRNAs species, particularly at higher temperatures. This was associated with a growth defect in yeast, thus offering a potential mechanism for the growth defects observed in patients with the mutation. The findings suggested that abnormal tRNA modification is a major contributor to disease pathogenesis.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2138 WDR4 Chirag Patel Classified gene: WDR4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2138 WDR4 Chirag Patel Gene: wdr4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2137 WDR4 Chirag Patel gene: WDR4 was added
gene: WDR4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to PubMed: 26416026, 30079490, 29597095, 28617965
Phenotypes for gene: WDR4 were set to Galloway-Mowat syndrome 6, OMIM #618347; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346
Review for gene: WDR4 was set to GREEN
Added comment: Galloway-Mowat syndrome 6, OMIM #618347:

1 family with 2 sibs with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 1 child with GMS and compound heterozygous mutations in the WDR4 gene, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed.

1 family with 4 sibs with GMS and homozygous splice site mutation in the WDR4 gene. Functional studies of the variant and studies of patient cells were not performed.



Microcephaly, growth deficiency, seizures, and brain malformations; OMIM #618346:

2 unrelated patients with intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Testing found the same homozygous missense mutation in the WDR4 gene, which segregated with the disorder in both families. Studies of patient cells and modeling of the corresponding mutation in yeast showed that the mutation caused a significant reduction in m(7)G46 methylation of specific tRNAs species, particularly at higher temperatures. This was associated with a growth defect in yeast, thus offering a potential mechanism for the growth defects observed in patients with the mutation. The findings suggested that abnormal tRNA modification is a major contributor to disease pathogenesis.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2136 XIST Chirag Patel Classified gene: XIST as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2136 XIST Chirag Patel Gene: xist has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2135 XIST Chirag Patel reviewed gene: XIST: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2135 YAP1 Chirag Patel Classified gene: YAP1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2135 YAP1 Chirag Patel Gene: yap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2134 YAP1 Chirag Patel reviewed gene: YAP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 24462371; Phenotypes: Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation, OMIM #120433; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2134 UNC13A Zornitza Stark Marked gene: UNC13A as ready
Intellectual disability syndromic and non-syndromic v0.2134 UNC13A Zornitza Stark Gene: unc13a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2134 WFS1 Chirag Patel changed review comment from: Very clear ID gene.; to: ID is a feature of condition, albeit rare.
Intellectual disability syndromic and non-syndromic v0.2134 UNC13A Zornitza Stark Publications for gene: UNC13A were set to
Intellectual disability syndromic and non-syndromic v0.2133 WFS1 Chirag Patel reviewed gene: WFS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wolfram syndrome 1, OMIM #222300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2133 VPS37A Chirag Patel Classified gene: VPS37A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2133 VPS37A Chirag Patel Gene: vps37a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2133 VPS37A Chirag Patel Classified gene: VPS37A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2133 VPS37A Chirag Patel Gene: vps37a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2132 USP18 Chirag Patel reviewed gene: USP18: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 31940699, 12833411, 27325888; Phenotypes: Pseudo-TORCH syndrome 2, OMIM #617397; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2132 MECP2 Michelle Torres reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301670; Phenotypes: Encephalopathy, neonatal severe 300673 XLR, Mental retardation, X-linked syndromic, Lubs type 300260 XLR, Mental retardation, X-linked, syndromic 13 300055 XLR, Rett syndrome 312750 XLD, Rett syndrome, atypical 312750 XLD, Rett syndrome, preserved speech variant 312750 XLD, {Autism susceptibility, X-linked 3} 300496 XL; Mode of inheritance: Other; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.2132 UPB1 Chirag Patel Classified gene: UPB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2132 UPB1 Chirag Patel Gene: upb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2132 UPB1 Chirag Patel Classified gene: UPB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2132 UPB1 Chirag Patel Gene: upb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2132 UPB1 Chirag Patel Classified gene: UPB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2132 UPB1 Chirag Patel Gene: upb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2131 UPB1 Chirag Patel reviewed gene: UPB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Beta-ureidopropionase deficiency, OMIM #613161; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2131 UFC1 Chirag Patel Classified gene: UFC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2131 UFC1 Chirag Patel Gene: ufc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2130 UFC1 Chirag Patel gene: UFC1 was added
gene: UFC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFC1 were set to PubMed: 29868776
Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth; OMIM #618076
Review for gene: UFC1 was set to GREEN
Added comment: 3 consanguineous Saudi families with neurodevelopmental disorder with spasticity and poor growth with a homozygous missense mutation in the UFC1 gene. An unrelated Swiss boy with same phenotype found to have a different homozygous mutation in the UFC1 gene. Total 8 patients from 4 families.

The mutations segregated with the disorder in the families. In vitro functional expression studies showed that both mutations caused impaired thioester binding with UFM1 (610553). Patient cells also showed decreased UFC1 intermediate formation with UFM1. The decrease in function was consistent with a hypomorphic allele, and Nahorski et al. (2018) suggested that complete loss of function would be embryonic lethal.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2129 UNC13A Zornitza Stark Phenotypes for gene: UNC13A were changed from to Congenital myasthenia; dyskinesia; autism; developmental delay
Intellectual disability syndromic and non-syndromic v0.2128 UNC13A Zornitza Stark Mode of inheritance for gene: UNC13A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2127 UNC13A Zornitza Stark Classified gene: UNC13A as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2127 UNC13A Zornitza Stark Gene: unc13a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2126 UNC13A Zornitza Stark reviewed gene: UNC13A: Rating: RED; Mode of pathogenicity: None; Publications: 27648472, 28192369; Phenotypes: Congenital myasthenia, dyskinesia, autism, developmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2126 PIGY Zornitza Stark reviewed gene: PIGY: Rating: AMBER; Mode of pathogenicity: None; Publications: 26293662; Phenotypes: Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2126 PIGP Zornitza Stark Marked gene: PIGP as ready
Intellectual disability syndromic and non-syndromic v0.2126 PIGP Zornitza Stark Gene: pigp has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2126 PIGP Zornitza Stark Classified gene: PIGP as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2126 PIGP Zornitza Stark Gene: pigp has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2125 PIGP Zornitza Stark gene: PIGP was added
gene: PIGP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PIGP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGP were set to 28334793; 31139695
Phenotypes for gene: PIGP were set to Epileptic encephalopathy, early infantile, 55, 617599
Review for gene: PIGP was set to AMBER
Added comment: Two unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2124 ZBTB11 Chirag Patel Classified gene: ZBTB11 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2124 ZBTB11 Chirag Patel Gene: zbtb11 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2123 ZBTB11 Chirag Patel reviewed gene: ZBTB11: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 29893856; Phenotypes: Intellectual developmental disorder, autosomal recessive 69, OMIM #618383; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2123 ZBTB16 Chirag Patel Classified gene: ZBTB16 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2123 ZBTB16 Chirag Patel Gene: zbtb16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2122 ZBTB16 Chirag Patel reviewed gene: ZBTB16: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 18611983; Phenotypes: Skeletal defects, genital hypoplasia, and mental retardation, OMIM #612447; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2122 PPP1R12A Zornitza Stark edited their review of gene: PPP1R12A: Changed rating: GREEN; Changed publications: 31883643
Intellectual disability syndromic and non-syndromic v0.2122 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease
Intellectual disability syndromic and non-syndromic v0.2121 ZBTB24 Chirag Patel reviewed gene: ZBTB24: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 21906047, 21596365, 23486536; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 2, OMIM # 614069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2121 SPTBN4 Bryony Thompson gene: SPTBN4 was added
gene: SPTBN4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SPTBN4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN4 were set to 28540413; 29861105
Phenotypes for gene: SPTBN4 were set to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519
Review for gene: SPTBN4 was set to GREEN
Added comment: 6 families with a severe neurological syndrome that includes congenital hypotonia, intellectual disability, and motor axonal and auditory neuropathy
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.2120 ZFHX3 Chirag Patel Classified gene: ZFHX3 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2120 ZFHX3 Chirag Patel Gene: zfhx3 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2119 ZFHX3 Chirag Patel reviewed gene: ZFHX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2119 ZNF81 Chirag Patel Classified gene: ZNF81 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.2119 ZNF81 Chirag Patel Gene: znf81 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2118 ZNF81 Chirag Patel reviewed gene: ZNF81: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 15121780; Phenotypes: mental retardation; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.2118 ZIC1 Chirag Patel Classified gene: ZIC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.2118 ZIC1 Chirag Patel Gene: zic1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2117 ZIC1 Chirag Patel gene: ZIC1 was added
gene: ZIC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: ZIC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZIC1 were set to PMID: 26340333, 30391508
Phenotypes for gene: ZIC1 were set to Structural brain anomalies with impaired intellectual development and craniosynostosis; OMIM #618736 
Review for gene: ZIC1 was set to GREEN
Added comment: 5 families with heterozygous mutations located in the final (third) exon of ZIC1 who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture.

2 sibs with BAIDCS, Vandervore et al. (2018) identified heterozygosity for a frameshift mutation in the ZIC1 gene. Neither parent had evidence of the mutation by whole-exome sequencing, suggesting that gonadal mosaicism for the mutation was present in one of the parents. Expression of the mutated allele was detected in patient fibroblasts by RT-PCR, evidence that the mutant mRNA did not undergo nonsense-mediated decay and probably generates an abnormal protein.


Also heterozygous deletions of ZIC1 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum. Loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.
Sources: Expert list