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Intellectual disability syndromic and non-syndromic v0.3078 MICU1 Zornitza Stark Marked gene: MICU1 as ready
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 v0.3069 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 v0.3068 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 Marked gene: EPG5 as ready
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 v0.3063 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
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 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 v0.3057 SON Zornitza Stark Marked gene: SON as ready
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 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 v0.3051 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 v0.3049 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 v0.3047 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 Phenotypes for gene: KPTN were changed from to Mental retardation, autosomal recessive 41 (MIM#615637)
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 Phenotypes for gene: TTI2 were changed from to Mental retardation, autosomal recessive 39 (MIM#615541) AR
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 v0.3035 ALG13 Zornitza Stark Marked gene: ALG13 as ready
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 v0.3026 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 v0.3025 UPF3B Zornitza Stark Marked gene: UPF3B as ready
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 v0.3022 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 v0.3017 TECPR2 Zornitza Stark Marked gene: TECPR2 as ready
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 v0.3014 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 v0.3013 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 v0.3012 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 v0.3009 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 v0.3007 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 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 v0.3006 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 Phenotypes for gene: KCNA2 were changed from to Early infantile encephalopathy 32, MIM#616366
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 v0.3000 DOCK3 Zornitza Stark Marked gene: DOCK3 as ready
Intellectual disability syndromic and non-syndromic v0.2997 ALDH5A1 Zornitza Stark Marked gene: ALDH5A1 as ready
Intellectual disability syndromic and non-syndromic v0.2994 SPRED1 Zornitza Stark Marked gene: SPRED1 as ready
Intellectual disability syndromic and non-syndromic v0.2991 SOS1 Zornitza Stark Marked gene: SOS1 as ready
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 v0.2987 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 v0.2985 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 v0.2983 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 v0.2982 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 v0.2979 HECW2 Zornitza Stark Marked gene: HECW2 as ready
Intellectual disability syndromic and non-syndromic v0.2976 NR2F1 Zornitza Stark Marked gene: NR2F1 as ready
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 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 v0.2971 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 v0.2967 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 v0.2964 GNB1 Zornitza Stark Marked gene: GNB1 as ready
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 v0.2961 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 v0.2960 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 v0.2958 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 EIF2S3 Zornitza Stark Marked gene: EIF2S3 as ready
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 v0.2951 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 v0.2950 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 v0.2949 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 Phenotypes for gene: PAK3 were changed from to Mental retardation, X-linked 30/47, MIM# 300558; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.2946 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 Phenotypes for gene: CLTC were changed from to Mental retardation, autosomal dominant 56, MIM# 617854
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 v0.2940 TRAPPC2L Zornitza Stark Marked gene: TRAPPC2L as ready
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 Phenotypes for gene: DPP6 were changed from to Mental retardation, autosomal dominant 33 (MIM#616311)
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 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 v0.2931 TRIT1 Zornitza Stark Marked gene: TRIT1 as ready
Intellectual disability syndromic and non-syndromic v0.2928 CREBBP Zornitza Stark Marked gene: CREBBP as ready
Intellectual disability syndromic and non-syndromic v0.2925 CDC6 Seb Lunke Marked gene: CDC6 as ready
Intellectual disability syndromic and non-syndromic v0.2921 CTNND1 Zornitza Stark Marked gene: CTNND1 as ready
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 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 v0.2914 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 v0.2911 KDM1A Zornitza Stark Marked gene: KDM1A as ready
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 v0.2908 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 v0.2905 AP4E1 Zornitza Stark Marked gene: AP4E1 as ready
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 v0.2902 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 v0.2897 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 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 v0.2891 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 v0.2888 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 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 v0.2885 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 v0.2882 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 v0.2878 ALG11 Zornitza Stark Marked gene: ALG11 as ready
Intellectual disability syndromic and non-syndromic v0.2875 PDE2A Zornitza Stark Marked gene: PDE2A as ready
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 Phenotypes for gene: CRADD were changed from to Mental retardation, autosomal recessive 34, with variant lissencephaly, MIM# 614499
Intellectual disability syndromic and non-syndromic v0.2870 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 TMTC3 Zornitza Stark Marked gene: TMTC3 as ready
Intellectual disability syndromic and non-syndromic v0.2867 MAOA Zornitza Stark Marked gene: MAOA as ready
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 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 v0.2861 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 Phenotypes for gene: GABRB3 were changed from to Epileptic encephalopathy, early infantile, 43, MIM# 617113
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 v0.2855 LMBRD2 Zornitza Stark Marked gene: LMBRD2 as ready
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 v0.2849 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 v0.2846 KANSL1 Zornitza Stark Marked gene: KANSL1 as ready
Intellectual disability syndromic and non-syndromic v0.2843 TAOK1 Zornitza Stark Marked gene: TAOK1 as ready
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 RAI1 Zornitza Stark Marked gene: RAI1 as ready
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 v0.2835 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 v0.2834 FAM50A Zornitza Stark Marked gene: FAM50A as ready
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 v0.2828 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 RAC1 Zornitza Stark Marked gene: RAC1 as ready
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 v0.2823 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 BCOR Zornitza Stark Marked gene: BCOR as ready
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 v0.2820 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 v0.2814 PIGQ Zornitza Stark Marked gene: PIGQ as ready
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 v0.2811 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 v0.2809 SCAF4 Zornitza Stark Marked gene: SCAF4 as ready
Intellectual disability syndromic and non-syndromic v0.2808 PJA1 Zornitza Stark Marked gene: PJA1 as ready
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 v0.2804 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 v0.2803 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 Phenotypes for gene: ASPM were changed from to Microcephaly 5, primary, autosomal recessive, MIM#608716
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 v0.2797 EEF1A2 Zornitza Stark Marked gene: EEF1A2 as ready
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 v0.2795 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 v0.2793 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 v0.2792 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 Marked gene: MORC2 as ready
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 v0.2783 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 v0.2779 NSDHL Zornitza Stark Marked gene: NSDHL as ready
Intellectual disability syndromic and non-syndromic v0.2774 DEAF1 Zornitza Stark Marked gene: DEAF1 as ready
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 Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3 (MIM#221750)
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 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 v0.2762 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 v0.2761 KIF21B Zornitza Stark Marked gene: KIF21B as ready
Intellectual disability syndromic and non-syndromic v0.2760 PAX1 Zornitza Stark Marked gene: PAX1 as ready
Intellectual disability syndromic and non-syndromic v0.2759 TMEM106B Zornitza Stark Marked gene: TMEM106B as ready
Intellectual disability syndromic and non-syndromic v0.2758 TBC1D2B Zornitza Stark Marked gene: TBC1D2B as ready
Intellectual disability syndromic and non-syndromic v0.2757 EXOC2 Zornitza Stark Marked gene: EXOC2 as ready
Intellectual disability syndromic and non-syndromic v0.2756 CEP120 Zornitza Stark Marked gene: CEP120 as ready
Intellectual disability syndromic and non-syndromic v0.2755 CCDC174 Zornitza Stark Marked gene: CCDC174 as ready
Intellectual disability syndromic and non-syndromic v0.2754 ACOX2 Zornitza Stark Marked gene: ACOX2 as ready
Intellectual disability syndromic and non-syndromic v0.2753 ABCA2 Zornitza Stark Marked gene: ABCA2 as ready
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 Phenotypes for gene: RPL10 were changed from to Mental retardation, X-linked, syndromic, 35 (MIM#300998)
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 v0.2744 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 Phenotypes for gene: PLCB1 were changed from to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
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 Phenotypes for gene: PIGY were changed from to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
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 v0.2734 RAP1GDS1 Zornitza Stark Marked gene: RAP1GDS1 as ready
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 v0.2731 SETD1B Zornitza Stark Marked gene: SETD1B as ready
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 v0.2726 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 HNRNPH1 Zornitza Stark Marked gene: HNRNPH1 as ready
Intellectual disability syndromic and non-syndromic v0.2725 PDCD6IP Zornitza Stark Marked gene: PDCD6IP as ready
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 v0.2722 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 v0.2720 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 v0.2716 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 v0.2712 UBE2A Zornitza Stark Marked gene: UBE2A as ready
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 v0.2709 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 Marked gene: GOLGA2 as ready
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 Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome (MIM#248800)
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 v0.2702 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
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 v0.2699 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 v0.2698 SCN3A Zornitza Stark Marked gene: SCN3A as ready
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 v0.2694 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 SLC6A1 Zornitza Stark Marked gene: SLC6A1 as ready
Intellectual disability syndromic and non-syndromic v0.2691 GATM Zornitza Stark Marked gene: GATM as ready
Intellectual disability syndromic and non-syndromic v0.2688 PSMB1 Zornitza Stark Marked gene: PSMB1 as ready
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 v0.2684 C16orf62 Zornitza Stark Marked gene: C16orf62 as ready
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 v0.2679 RBL2 Zornitza Stark Marked gene: RBL2 as ready
Intellectual disability syndromic and non-syndromic v0.2678 GRM7 Zornitza Stark Marked gene: GRM7 as ready
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 v0.2674 OTUD7A Zornitza Stark Marked gene: OTUD7A as ready
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 Phenotypes for gene: GATAD2B were changed from to Mental retardation, autosomal dominant 18, OMIM # 615074
Intellectual disability syndromic and non-syndromic v0.2671 KMT2D Zornitza Stark Marked gene: KMT2D as ready
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 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 v0.2659 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 v0.2658 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 v0.2657 HIST1H4J Sue White Marked gene: HIST1H4J as ready
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 v0.2655 ADAM22 Zornitza Stark Marked gene: ADAM22 as ready
Intellectual disability syndromic and non-syndromic v0.2655 RAX Zornitza Stark Marked gene: RAX as ready
Intellectual disability syndromic and non-syndromic v0.2655 TUBA8 Zornitza Stark Marked gene: TUBA8 as ready
Intellectual disability syndromic and non-syndromic v0.2655 XIST Zornitza Stark Marked gene: XIST as ready
Intellectual disability syndromic and non-syndromic v0.2655 WFS1 Zornitza Stark Marked gene: WFS1 as ready
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 Phenotypes for gene: RBM10 were changed from to TARP syndrome, 311900 (3), X-linked recessive
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 v0.2649 DHX30 Zornitza Stark Marked gene: DHX30 as ready
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 Phenotypes for gene: TRIP12 were changed from to Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752
Intellectual disability syndromic and non-syndromic v0.2641 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 v0.2640 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 PACS1 Zornitza Stark Marked gene: PACS1 as ready
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 Phenotypes for gene: PRKD1 were changed from to Congenital heart defects and ectodermal dysplasia, 617364
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 v0.2631 CUL3 Zornitza Stark Marked gene: CUL3 as ready
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 v0.2629 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 v0.2627 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 v0.2626 YIF1B Zornitza Stark Marked gene: YIF1B as ready
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 v0.2621 CDC42BPB Zornitza Stark Marked gene: CDC42BPB as ready
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 Marked gene: EMX2 as ready
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 v0.2602 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 v0.2600 VPS51 Zornitza Stark Marked gene: VPS51 as ready
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 CDK19 Zornitza Stark Marked gene: CDK19 as ready
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 v0.2592 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 v0.2590 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 v0.2589 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 v0.2587 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 v0.2585 TAF1 Zornitza Stark Marked gene: TAF1 as ready
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 v0.2582 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 Phenotypes for gene: KCNB1 were changed from to Epileptic encephalopathy, early infantile, 26, MIM# 616056
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 v0.2575 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: 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 v0.2574 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 Phenotypes for gene: PLPBP were changed from to Epilepsy, early-onset, vitamin B6-dependent, MIM# 617290
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 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 v0.2566 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 Phenotypes for gene: TSEN34 were changed from to Pontocerebellar hypoplasia type 2C, MIM# 612390
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 v0.2561 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Intellectual disability syndromic and non-syndromic v0.2558 TLK2 Zornitza Stark Marked gene: TLK2 as ready
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 Phenotypes for gene: DYRK1A were changed from to Mental retardation, autosomal dominant 7 (MIM#614104)
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 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 v0.2549 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 v0.2548 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 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 v0.2546 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 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 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 GSX2 Zornitza Stark Marked gene: GSX2 as ready
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 v0.2540 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 v0.2536 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 Phenotypes for gene: CTCF were changed from to Mental retardation, autosomal dominant 21 (MIM#615502)
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 v0.2531 ZMYND11 Zornitza Stark Marked gene: ZMYND11 as ready
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 v0.2528 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 v0.2527 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 v0.2525 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 SLC18A2 Zornitza Stark Marked gene: SLC18A2 as ready
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 NRROS Zornitza Stark Marked gene: NRROS as ready
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 v0.2518 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 Phenotypes for gene: AP3B2 were changed from to Early-onset epileptic encephalopathy with optic atrophy, MIM#617276
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 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 v0.2512 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 v0.2511 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 v0.2509 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 v0.2507 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 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 v0.2504 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 v0.2502 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 v0.2495 DLG3 Zornitza Stark Marked gene: DLG3 as ready
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 v0.2492 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 v0.2491 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 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 v0.2489 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 v0.2487 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 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 v0.2484 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 v0.2482 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 v0.2479 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 Marked gene: CNOT3 as ready
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 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 Marked gene: SPATA5 as ready
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 v0.2470 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 v0.2469 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 v0.2467 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 Phenotypes for gene: GPT2 were changed from to Mental retardation, autosomal recessive 49, MIM#616281
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 v0.2462 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 v0.2460 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 v0.2457 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 v0.2456 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 v0.2453 RPS23 Zornitza Stark Marked gene: RPS23 as ready
Intellectual disability syndromic and non-syndromic v0.2449 RNF13 Zornitza Stark Marked gene: RNF13 as ready
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 v0.2443 RHEB Zornitza Stark Marked gene: RHEB as ready
Intellectual disability syndromic and non-syndromic v0.2440 MRPS34 Zornitza Stark Marked gene: MRPS34 as ready
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 MFSD2A Zornitza Stark Marked gene: MFSD2A as ready
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 v0.2431 MCM3AP Zornitza Stark Marked gene: MCM3AP as ready
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 v0.2427 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 Phenotypes for gene: PURA were changed from to Mental retardation, autosomal dominant 31, MIM# 616158
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 v0.2420 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 Phenotypes for gene: TRIO were changed from to Mental retardation, autosomal dominant 44, MIM# 617061
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 Phenotypes for gene: MAN1B1 were changed from to Mental retardation, autosomal recessive 15, MIM#614202
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 v0.2413 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 NUDT2 Zornitza Stark Marked gene: NUDT2 as ready
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 NKAP Zornitza Stark Marked gene: NKAP as ready
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 Phenotypes for gene: NHP2 were changed from to Dyskeratosis congenita, autosomal recessive 2, MIM# 613987; Høyeraal-Hreidarsson syndrome
Intellectual disability syndromic and non-syndromic v0.2405 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 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 v0.2401 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 Phenotypes for gene: NGF were changed from to Neuropathy, hereditary sensory and autonomic, type V, MIM# 608654
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 v0.2397 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 v0.2395 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 v0.2394 TBR1 Zornitza Stark Marked gene: TBR1 as ready
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 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 v0.2388 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 v0.2387 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 v0.2386 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 NDUFAF5 Zornitza Stark Marked gene: NDUFAF5 as ready
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 v0.2382 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 v0.2381 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 v0.2379 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 v0.2377 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 v0.2374 NBN Zornitza Stark Marked gene: NBN as ready
Intellectual disability syndromic and non-syndromic v0.2371 ZBTB24 Zornitza Stark Marked gene: ZBTB24 as ready
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 Phenotypes for gene: ZBTB16 were changed from to Skeletal defects, genital hypoplasia, and mental retardation, OMIM #612447
Intellectual disability syndromic and non-syndromic v0.2365 ZBTB11 Zornitza Stark Marked gene: ZBTB11 as ready
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 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 v0.2355 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 Marked gene: WDR4 as ready
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 v0.2350 TUBGCP4 Zornitza Stark Marked gene: TUBGCP4 as ready
Intellectual disability syndromic and non-syndromic v0.2344 TSHR Zornitza Stark Marked gene: TSHR as ready
Intellectual disability syndromic and non-syndromic v0.2340 TSEN15 Zornitza Stark Marked gene: TSEN15 as ready
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 Phenotypes for gene: TRIP13 were changed from to Mosaic variegated aneuploidy syndrome 3, MIM# 617598
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 v0.2333 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 Phenotypes for gene: TRAK1 were changed from to Epileptic encephalopathy, early infantile, 68, MIM# 618201
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 v0.2328 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 v0.2324 TPH2 Zornitza Stark Marked gene: TPH2 as ready
Intellectual disability syndromic and non-syndromic v0.2320 SPOP Zornitza Stark Marked gene: SPOP as ready
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 Phenotypes for gene: TNIK were changed from to Mental retardation, autosomal recessive 54, MIM# 617028
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 v0.2310 TMEM94 Zornitza Stark Marked gene: TMEM94 as ready
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 Phenotypes for gene: TMEM260 were changed from to Structural heart defects and renal anomalies syndrome, MIM# 617478
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 v0.2303 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 v0.2300 TIMM50 Zornitza Stark Marked gene: TIMM50 as ready
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 Marked gene: THRB as ready
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 v0.2289 TECR Zornitza Stark Marked gene: TECR as ready
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 v0.2285 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 v0.2281 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 Phenotypes for gene: TAF2 were changed from to Mental retardation, autosomal recessive 40, MIM# 615599
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 v0.2276 TAF13 Zornitza Stark Phenotypes for gene: TAF13 were changed from to Mental retardation, autosomal recessive 60, MIM# 617432
Intellectual disability syndromic and non-syndromic v0.2273 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 Phenotypes for gene: SYT14 were changed from to Spinocerebellar ataxia, autosomal recessive 11, MIM# 614229
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 v0.2267 SUFU Zornitza Stark Marked gene: SUFU as ready
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 v0.2262 STRADA Zornitza Stark Marked gene: STRADA as ready
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 Phenotypes for gene: SRPX2 were changed from to Rolandic epilepsy, mental retardation, and speech dyspraxia, MIM# 300643
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 v0.2252 KMT2A Zornitza Stark Marked gene: KMT2A as ready
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 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 v0.2247 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 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 v0.2244 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 v0.2243 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 Phenotypes for gene: SPAST were changed from to Spastic paraplegia 4, autosomal dominant, MIM# 182601
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 v0.2238 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 v0.2237 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 v0.2235 SOBP Zornitza Stark Marked gene: SOBP as ready
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 v0.2231 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 v0.2230 SNIP1 Zornitza Stark Marked gene: SNIP1 as ready
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 v0.2226 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 v0.2225 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 v0.2219 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 v0.2216 SLC7A7 Zornitza Stark Marked gene: SLC7A7 as ready
Intellectual disability syndromic and non-syndromic v0.2213 SLC6A4 Zornitza Stark Marked gene: SLC6A4 as ready
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 v0.2206 SLC25A24 Zornitza Stark Marked gene: SLC25A24 as ready
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 SLC1A2 Zornitza Stark Marked gene: SLC1A2 as ready
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 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 v0.2196 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 v0.2194 INTS1 Zornitza Stark Marked gene: INTS1 as ready
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 v0.2191 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 v0.2190 SACS Zornitza Stark Marked gene: SACS as ready
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 v0.2186 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 Marked gene: SOX3 as ready
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 v0.2181 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 v0.2178 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 PTRHD1 Zornitza Stark Marked gene: PTRHD1 as ready
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 v0.2175 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 v0.2170 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 v0.2166 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 Marked gene: PRRT2 as ready
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 v0.2163 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 Phenotypes for gene: POU1F1 were changed from to Pituitary hormone deficiency, combined, 1, MIM# 613038
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 v0.2159 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 v0.2157 PMPCA Zornitza Stark Marked gene: PMPCA as ready
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 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 v0.2152 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 v0.2151 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 v0.2149 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 v0.2147 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 v0.2145 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 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 v0.2141 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 v0.2137 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 v0.2134 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 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 v0.2132 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 v0.2126 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 v0.2125 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 v0.2122 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 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease
Intellectual disability syndromic and non-syndromic v0.2118 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 v0.2117 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
Intellectual disability syndromic and non-syndromic v0.2115 ZNF148 Chirag Patel gene: ZNF148 was added
gene: ZNF148 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: ZNF148 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF148 were set to PMID: 27964749
Phenotypes for gene: ZNF148 were set to Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies; OMIM #617260
Review for gene: ZNF148 was set to GREEN
Added comment: 4 patients with de novo heterozygous nonsense or frameshift mutations in the ZNF148 gene. Patients characterized by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. No functional evidence.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2114 EML1 Zornitza Stark Marked gene: EML1 as ready
Intellectual disability syndromic and non-syndromic v0.2111 WAC Zornitza Stark Marked gene: WAC as ready
Intellectual disability syndromic and non-syndromic v0.2108 GLS Zornitza Stark edited their review of gene: GLS: Added comment: In addition, single individual also reported with de novo, GoF variant with profound ID, cataract.; Changed mode of pathogenicity: Other; Changed publications: 30970188, 30239721; Changed phenotypes: Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2108 PIGH Zornitza Stark Marked gene: PIGH as ready
Intellectual disability syndromic and non-syndromic v0.2105 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Intellectual disability syndromic and non-syndromic v0.2105 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from Marden-Walker syndrome, MIM# 248700; Arthrogryposis, distal, type 3, MIM# 114300 to Marden-Walker syndrome, MIM# 248700; Arthrogryposis, distal, type 3, MIM# 114300
Intellectual disability syndromic and non-syndromic v0.2103 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from Marden-Walker syndrome, MIM# 248700; Arthrogryposis, distal, type 3, MIM# 114300 to Marden-Walker syndrome, MIM# 248700; Arthrogryposis, distal, type 3, MIM# 114300
Intellectual disability syndromic and non-syndromic v0.2103 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from to Marden-Walker syndrome, MIM# 248700; Arthrogryposis, distal, type 3, MIM# 114300
Intellectual disability syndromic and non-syndromic v0.2101 PIEZO2 Zornitza Stark reviewed gene: PIEZO2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24726473; Phenotypes: Marden-Walker syndrome, MIM# 248700, Arthrogryposis, distal, type 3, MIM# 114300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2101 PHACTR1 Zornitza Stark Marked gene: PHACTR1 as ready
Intellectual disability syndromic and non-syndromic v0.2101 PHACTR1 Zornitza Stark Phenotypes for gene: PHACTR1 were changed from Seizures:Epileptic encephalopathy, early infantile, 70, MIM# 618298; PHACTR1-associated neurodevelopment disorder to Epileptic encephalopathy, early infantile, 70, MIM# 618298; PHACTR1-associated neurodevelopment disorder
Intellectual disability syndromic and non-syndromic v0.2099 PHACTR1 Zornitza Stark gene: PHACTR1 was added
gene: PHACTR1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PHACTR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHACTR1 were set to 30256902; 28135719; 23033978; 27457812
Phenotypes for gene: PHACTR1 were set to Seizures:Epileptic encephalopathy, early infantile, 70, MIM# 618298; PHACTR1-associated neurodevelopment disorder
Penetrance for gene: PHACTR1 were set to Incomplete
Mode of pathogenicity for gene: PHACTR1 was set to Other
Review for gene: PHACTR1 was set to GREEN
gene: PHACTR1 was marked as current diagnostic
Added comment: 6 unrelated individuals reported altogether with variants in this gene. Several as part of large cohorts, so limited variant and patient characterisation. One variant reported by de Ligt et al is present in the population (4 individuals) suggesting reduced penetrance. However, functional data (including mouse model) for this and other variants exerting a dominant negative effect.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2098 PET100 Zornitza Stark Marked gene: PET100 as ready
Intellectual disability syndromic and non-syndromic v0.2092 PCDH10 Zornitza Stark Marked gene: PCDH10 as ready
Intellectual disability syndromic and non-syndromic v0.2087 PAX7 Zornitza Stark Marked gene: PAX7 as ready
Intellectual disability syndromic and non-syndromic v0.2084 OSGEP Zornitza Stark Marked gene: OSGEP as ready
Intellectual disability syndromic and non-syndromic v0.2083 OSGEP Zornitza Stark gene: OSGEP was added
gene: OSGEP was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: OSGEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OSGEP were set to 28805828; 28272532
Phenotypes for gene: OSGEP were set to Galloway-Mowat syndrome 3, MIM# 617729
Review for gene: OSGEP was set to GREEN
gene: OSGEP was marked as current diagnostic
Added comment: 25 families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2082 ORC1 Zornitza Stark Marked gene: ORC1 as ready
Intellectual disability syndromic and non-syndromic v0.2080 LYST Zornitza Stark changed review comment from: Review in light of Genomics England curator assessments: More commonly progressive movement disorder; rare reports of true IDincluding in a patient where both parents had ID, raising possibility of alternative cause. Downgrade to Amber.; to: Review in light of Genomics England curator assessments: More commonly progressive movement disorder; rare reports of true ID including in a patient where both parents had ID, raising possibility of alternative cause. Downgrade to Amber.
Intellectual disability syndromic and non-syndromic v0.2079 LYST Zornitza Stark commented on gene: LYST: Review in light of Genomics England curator assessments: More commonly progressive movement disorder; rare reports of true IDincluding in a patient where both parents had ID, raising possibility of alternative cause. Downgrade to Amber.
Intellectual disability syndromic and non-syndromic v0.2079 LRP5 Zornitza Stark Marked gene: LRP5 as ready
Intellectual disability syndromic and non-syndromic v0.2077 LNPK Zornitza Stark Marked gene: LNPK as ready
Intellectual disability syndromic and non-syndromic v0.2073 LMBRD1 Zornitza Stark Marked gene: LMBRD1 as ready
Intellectual disability syndromic and non-syndromic v0.2071 LIPT2 Zornitza Stark Marked gene: LIPT2 as ready
Intellectual disability syndromic and non-syndromic v0.2069 LAS1L Zornitza Stark Marked gene: LAS1L as ready
Intellectual disability syndromic and non-syndromic v0.2067 KIF4A Zornitza Stark Marked gene: KIF4A as ready
Intellectual disability syndromic and non-syndromic v0.2067 KIF4A Zornitza Stark Phenotypes for gene: KIF4A were changed from to Mental retardation, X-linked 100, MIM# 300923
Intellectual disability syndromic and non-syndromic v0.2064 KIF4A Zornitza Stark reviewed gene: KIF4A: Rating: RED; Mode of pathogenicity: None; Publications: 24812067; Phenotypes: Mental retardation, X-linked 100, MIM# 300923; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2064 KIF2A Zornitza Stark Marked gene: KIF2A as ready
Intellectual disability syndromic and non-syndromic v0.2063 KIF2A Zornitza Stark gene: KIF2A was added
gene: KIF2A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: KIF2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF2A were set to 23603762; 21594994; 27747449; 27896282
Phenotypes for gene: KIF2A were set to Cortical dysplasia, complex, with other brain malformations 3, 615411
Review for gene: KIF2A was set to GREEN
gene: KIF2A was marked as current diagnostic
Added comment: Five unrelated individuals reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2062 KCNT2 Zornitza Stark Marked gene: KCNT2 as ready
Intellectual disability syndromic and non-syndromic v0.2061 KCNT2 Zornitza Stark gene: KCNT2 was added
gene: KCNT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: KCNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNT2 were set to 29069600; 29740868
Phenotypes for gene: KCNT2 were set to Epileptic encephalopathy, early infantile 57, 617771
Mode of pathogenicity for gene: KCNT2 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: KCNT2 was set to GREEN
gene: KCNT2 was marked as current diagnostic
Added comment: Three unrelated individuals reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2060 KCNK4 Zornitza Stark Marked gene: KCNK4 as ready
Intellectual disability syndromic and non-syndromic v0.2059 KCNK4 Zornitza Stark gene: KCNK4 was added
gene: KCNK4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: KCNK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNK4 were set to 30290154
Phenotypes for gene: KCNK4 were set to Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome 618381
Mode of pathogenicity for gene: KCNK4 was set to Other
Review for gene: KCNK4 was set to GREEN
Added comment: Three unrelated individuals reported with a distinctive syndromic ID condition and de novo variants (two of the individuals had the same variant). Likely GoF as KO mice do not share the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2056 KATNAL2 Zornitza Stark Marked gene: KATNAL2 as ready
Intellectual disability syndromic and non-syndromic v0.2054 ITGA7 Zornitza Stark Marked gene: ITGA7 as ready
Intellectual disability syndromic and non-syndromic v0.2053 ITGA7 Zornitza Stark Phenotypes for gene: ITGA7 were changed from to Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204
Intellectual disability syndromic and non-syndromic v0.2050 ITGA7 Zornitza Stark reviewed gene: ITGA7: Rating: AMBER; Mode of pathogenicity: None; Publications: 9590299; Phenotypes: Muscular dystrophy, congenital, due to ITGA7 deficiency, MIM# 613204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2050 ISCA2 Zornitza Stark Marked gene: ISCA2 as ready
Intellectual disability syndromic and non-syndromic v0.2047 INTS8 Zornitza Stark Marked gene: INTS8 as ready
Intellectual disability syndromic and non-syndromic v0.2047 INTS8 Zornitza Stark Phenotypes for gene: INTS8 were changed from to Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, MIM# 618572
Intellectual disability syndromic and non-syndromic v0.2043 INTS8 Zornitza Stark reviewed gene: INTS8: Rating: RED; Mode of pathogenicity: None; Publications: 28542170; Phenotypes: Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, MIM# 618572; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2043 INSR Zornitza Stark Marked gene: INSR as ready
Intellectual disability syndromic and non-syndromic v0.2040 TRAPPC9 Zornitza Stark Marked gene: TRAPPC9 as ready
Intellectual disability syndromic and non-syndromic v0.2038 IGBP1 Zornitza Stark Phenotypes for gene: IGBP1 were changed from Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia, MIM# 300472 to Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia, MIM# 300472
Intellectual disability syndromic and non-syndromic v0.2037 IGBP1 Zornitza Stark Marked gene: IGBP1 as ready
Intellectual disability syndromic and non-syndromic v0.2037 IGBP1 Zornitza Stark Phenotypes for gene: IGBP1 were changed from to Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia, MIM# 300472
Intellectual disability syndromic and non-syndromic v0.2035 IGBP1 Zornitza Stark reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: 14556245; Phenotypes: Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia, MIM# 300472; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.2035 IQSEC2 Zornitza Stark reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31415821, 20473311, 30842726; Phenotypes: Mental retardation, X-linked 1/78, MIM#309530; 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 v0.2035 HTT Zornitza Stark Marked gene: HTT as ready
Intellectual disability syndromic and non-syndromic v0.2034 HTT Zornitza Stark gene: HTT was added
gene: HTT was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: HTT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HTT were set to 26740508; 27329733
Phenotypes for gene: HTT were set to Lopes-Maciel-Rodan syndrome, 617435; LOMARS; Intellectual disability
Review for gene: HTT was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants in this gene and a neurodevelopmental phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2032 HIST1H4C Zornitza Stark Marked gene: HIST1H4C as ready
Intellectual disability syndromic and non-syndromic v0.2029 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Intellectual disability syndromic and non-syndromic v0.2029 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from Mental retardation, autosomal recessive 38, MIM# 615516 to Mental retardation, autosomal recessive 38, MIM# 615516
Intellectual disability syndromic and non-syndromic v0.2027 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38, MIM# 615516
Intellectual disability syndromic and non-syndromic v0.2024 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23243086, 23065719; Phenotypes: Mental retardation, autosomal recessive 38 615516; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2024 HAX1 Zornitza Stark Marked gene: HAX1 as ready
Intellectual disability syndromic and non-syndromic v0.2021 HARS2 Zornitza Stark Phenotypes for gene: HARS2 were changed from Perrault syndrome 2, MIM# 614926 to Perrault syndrome 2, MIM# 614926
Intellectual disability syndromic and non-syndromic v0.2021 HARS2 Zornitza Stark Marked gene: HARS2 as ready
Intellectual disability syndromic and non-syndromic v0.2021 HARS2 Zornitza Stark Gene: hars2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2021 HARS2 Zornitza Stark Phenotypes for gene: HARS2 were changed from Perrault syndrome 2, MIM# 614926 to Perrault syndrome 2, MIM# 614926
Intellectual disability syndromic and non-syndromic v0.2020 HARS2 Zornitza Stark Phenotypes for gene: HARS2 were changed from to Perrault syndrome 2, MIM# 614926
Intellectual disability syndromic and non-syndromic v0.2020 HARS2 Zornitza Stark Publications for gene: HARS2 were set to
Intellectual disability syndromic and non-syndromic v0.2019 HARS2 Zornitza Stark Mode of inheritance for gene: HARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2018 HARS2 Zornitza Stark Classified gene: HARS2 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.2018 HARS2 Zornitza Stark Gene: hars2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.2017 HARS2 Zornitza Stark reviewed gene: HARS2: Rating: RED; Mode of pathogenicity: None; Publications: 21464306, 27650058, 31827252, 31486067; Phenotypes: Perrault syndrome 2, MIM# 614926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2017 GTF3C3 Zornitza Stark Marked gene: GTF3C3 as ready
Intellectual disability syndromic and non-syndromic v0.2013 KIF11 Zornitza Stark Marked gene: KIF11 as ready
Intellectual disability syndromic and non-syndromic v0.2013 KIF11 Zornitza Stark Phenotypes for gene: KIF11 were changed from to Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation MIM#152950
Intellectual disability syndromic and non-syndromic v0.2011 GSS Zornitza Stark Marked gene: GSS as ready
Intellectual disability syndromic and non-syndromic v0.2008 GRIN2D Zornitza Stark Marked gene: GRIN2D as ready
Intellectual disability syndromic and non-syndromic v0.2007 GRIN2D Zornitza Stark gene: GRIN2D was added
gene: GRIN2D was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: GRIN2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2D were set to 27616483; 30280376
Phenotypes for gene: GRIN2D were set to Epileptic encephalopathy, early infantile, 46, MIM# 617162; intellectual disability
Mode of pathogenicity for gene: GRIN2D was set to Other
Review for gene: GRIN2D was set to GREEN
gene: GRIN2D was marked as current diagnostic
Added comment: Five unrelated individuals reported, two with recurrent variant (NM_000836.2:c.1999G>A or p.Val667Ile). GoF postulated as mechanism.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2006 KIF11 Ee Ming Wong reviewed gene: KIF11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27212378, 24281367; Phenotypes: 1. Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (OMIM), 2. Familial exudative vitreoretinopathy (FEVR) (PMID: 27212378); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.2006 GRIA1 Zornitza Stark Marked gene: GRIA1 as ready
Intellectual disability syndromic and non-syndromic v0.2005 GRIA1 Zornitza Stark gene: GRIA1 was added
gene: GRIA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: GRIA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178
Phenotypes for gene: GRIA1 were set to Intellectual disability; autism
Review for gene: GRIA1 was set to GREEN
Added comment: Multiple affected individuals reported but in large ID cohorts reporting multiple candidate genes. Recurrent (p.A636T) variant.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2002 GPHN Zornitza Stark edited their review of gene: GPHN: Added comment: Only two families reported with bi-allelic variants. Also note reports of mono-allelic deletions associated with ID/autism/SZ.; Changed rating: AMBER; Changed publications: 22040219, 26613940, 24561070, 23393157; Changed phenotypes: Molybdenum cofactor deficiency C, MIM#615501, intellectual disability; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2001 MARS2 Zornitza Stark Marked gene: MARS2 as ready
Intellectual disability syndromic and non-syndromic v0.2001 MARS2 Zornitza Stark Gene: mars2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.2001 HDAC4 Zornitza Stark Marked gene: HDAC4 as ready
Intellectual disability syndromic and non-syndromic v0.2001 HDAC4 Zornitza Stark Phenotypes for gene: HDAC4 were changed from Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability to Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability
Intellectual disability syndromic and non-syndromic v0.2000 HDAC4 Zornitza Stark Phenotypes for gene: HDAC4 were changed from to Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability
Intellectual disability syndromic and non-syndromic v0.1997 HDAC4 Zornitza Stark reviewed gene: HDAC4: Rating: AMBER; Mode of pathogenicity: None; Publications: 24715439, 20691407, 31209962; Phenotypes: Brachydactyly mental retardation syndrome, Brachydactyly without intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1997 UBR4 Zornitza Stark Marked gene: UBR4 as ready
Intellectual disability syndromic and non-syndromic v0.1992 GMNN Zornitza Stark Marked gene: GMNN as ready
Intellectual disability syndromic and non-syndromic v0.1990 TRAPPC4 Zornitza Stark Marked gene: TRAPPC4 as ready
Intellectual disability syndromic and non-syndromic v0.1989 TRAPPC4 Zornitza Stark gene: TRAPPC4 was added
gene: TRAPPC4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: TRAPPC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC4 were set to 31794024
Phenotypes for gene: TRAPPC4 were set to intellectual disability; epilepsy; spasticity; microcephaly
Review for gene: TRAPPC4 was set to GREEN
Added comment: Seven individuals from three unrelated families reported; recurrent splice site variant (hg19:chr11:g.118890966A>G; TRAPPC4: NM_016146.5; c.454+3A>G), not a founder variant.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.1988 SNX27 Zornitza Stark Marked gene: SNX27 as ready
Intellectual disability syndromic and non-syndromic v0.1986 PMPCB Zornitza Stark Marked gene: PMPCB as ready
Intellectual disability syndromic and non-syndromic v0.1984 NSF Zornitza Stark Marked gene: NSF as ready
Intellectual disability syndromic and non-syndromic v0.1983 NSF Zornitza Stark gene: NSF was added
gene: NSF was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSF were set to 31675180
Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability
Review for gene: NSF was set to AMBER
Added comment: Two individuals reported with de novo missense variants in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1982 KAT8 Zornitza Stark Marked gene: KAT8 as ready
Intellectual disability syndromic and non-syndromic v0.1981 KAT8 Zornitza Stark gene: KAT8 was added
gene: KAT8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KAT8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT8 were set to 31794431
Phenotypes for gene: KAT8 were set to Intellectual disability; seizures; autism; dysmorphic features
Review for gene: KAT8 was set to GREEN
Added comment: Eight unrelated individuals reported with de novo variants in this gene and a mouse model. All variants missense, in the chromobarrel domain or the acetyltransferase domain; three individuals had the same variant p.Tyr90Cys . One more individual reported with bi-allelic variants: one missense and one frameshift; carrier parents were normal suggesting that may be haploinsuffiency is not the mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1980 GLRA1 Zornitza Stark Marked gene: GLRA1 as ready
Intellectual disability syndromic and non-syndromic v0.1977 GJB1 Zornitza Stark edited their review of gene: GJB1: Added comment: PMID 26385972 reports cognitive impairment in 4 adult cases and PMID 23279342 reports a proband and her sister with severe neuropathy and subclinical cognitive impairment, while the proband's brother showed severe cognitive impairment and mild neuropathy. Based on the current evidence, ID does not appear to be a prominent or consistent part of the phenotype of this neuropathy.; Changed publications: 26385972, 23279342
Intellectual disability syndromic and non-syndromic v0.1977 GEMIN4 Zornitza Stark Marked gene: GEMIN4 as ready
Intellectual disability syndromic and non-syndromic v0.1977 GEMIN4 Zornitza Stark Phenotypes for gene: GEMIN4 were changed from to Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, MIM# 617913
Intellectual disability syndromic and non-syndromic v0.1975 GEMIN4 Zornitza Stark reviewed gene: GEMIN4: Rating: AMBER; Mode of pathogenicity: None; Publications: 25558065, 30237576; Phenotypes: Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities, MIM# 617913; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1975 GBA Zornitza Stark Marked gene: GBA as ready
Intellectual disability syndromic and non-syndromic v0.1972 GAN Zornitza Stark Marked gene: GAN as ready
Intellectual disability syndromic and non-syndromic v0.1969 GABRA2 Zornitza Stark Marked gene: GABRA2 as ready
Intellectual disability syndromic and non-syndromic v0.1968 GABRA2 Zornitza Stark gene: GABRA2 was added
gene: GABRA2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: GABRA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA2 were set to 29422393; 29961870; 31032849; 31032848
Phenotypes for gene: GABRA2 were set to Epileptic encephalopathy, early infantile, 78, 618557
Review for gene: GABRA2 was set to GREEN
gene: GABRA2 was marked as current diagnostic
Added comment: Six unrelated families reported, ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1967 GABBR2 Zornitza Stark Marked gene: GABBR2 as ready
Intellectual disability syndromic and non-syndromic v0.1966 GABBR2 Zornitza Stark gene: GABBR2 was added
gene: GABBR2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: GABBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABBR2 were set to 29100083; 28061363; 28135719; 28856709; 29369404; 29377213
Phenotypes for gene: GABBR2 were set to Neurodevelopmental disorder with poor language and loss of hand skills, 617903
Review for gene: GABBR2 was set to GREEN
gene: GABBR2 was marked as current diagnostic
Added comment: At least 7 unrelated individuals reported, missense variants only, A707T and A567T (recurrent).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1965 HNRNPU Zornitza Stark Phenotypes for gene: HNRNPU were changed from to Epileptic encephalopathy, early infantile, 54, MIM#617391
Intellectual disability syndromic and non-syndromic v0.1962 HNRNPU Zornitza Stark reviewed gene: HNRNPU: Rating: GREEN; Mode of pathogenicity: None; Publications: 28944577, 28393272; Phenotypes: Epileptic encephalopathy, early infantile, 54, MIM#617391; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1962 G6PC3 Zornitza Stark Marked gene: G6PC3 as ready
Intellectual disability syndromic and non-syndromic v0.1958 EHMT1 Zornitza Stark Marked gene: EHMT1 as ready
Intellectual disability syndromic and non-syndromic v0.1955 FTO Zornitza Stark Marked gene: FTO as ready
Intellectual disability syndromic and non-syndromic v0.1955 FTO Zornitza Stark Phenotypes for gene: FTO were changed from Growth retardation, developmental delay, facial dysmorphism, MIM# 612938 to Growth retardation, developmental delay, facial dysmorphism, MIM# 612938
Intellectual disability syndromic and non-syndromic v0.1953 FTO Zornitza Stark Phenotypes for gene: FTO were changed from to Growth retardation, developmental delay, facial dysmorphism, MIM# 612938
Intellectual disability syndromic and non-syndromic v0.1950 FTO Zornitza Stark reviewed gene: FTO: Rating: ; Mode of pathogenicity: None; Publications: 19559399, 26378117; Phenotypes: Growth retardation, developmental delay, facial dysmorphism, MIM# 612938; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1950 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Intellectual disability syndromic and non-syndromic v0.1949 FRRS1L Zornitza Stark gene: FRRS1L was added
gene: FRRS1L was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: FRRS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRRS1L were set to 27236917; 27239025
Phenotypes for gene: FRRS1L were set to Epileptic encephalopathy, early infantile, 37, MIM#616981
Review for gene: FRRS1L was set to GREEN
Added comment: Five unrelated individuals reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1948 FIBP Zornitza Stark Marked gene: FIBP as ready
Intellectual disability syndromic and non-syndromic v0.1945 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
Intellectual disability syndromic and non-syndromic v0.1945 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Hartsfield syndrome, MIM# 615465
Intellectual disability syndromic and non-syndromic v0.1942 FGFR3 Zornitza Stark Marked gene: FGFR3 as ready
Intellectual disability syndromic and non-syndromic v0.1940 FGFR1 Zornitza Stark reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23812909; Phenotypes: Hartsfield syndrome, MIM# 615465; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1940 TKFC Zornitza Stark Marked gene: TKFC as ready
Intellectual disability syndromic and non-syndromic v0.1939 TKFC Zornitza Stark gene: TKFC was added
gene: TKFC was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 32004446
Phenotypes for gene: TKFC were set to Developmental delay; cataracts; liver dysfunction
Review for gene: TKFC was set to AMBER
Added comment: Two unrelated individuals reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1938 RALGAPA1 Zornitza Stark Marked gene: RALGAPA1 as ready
Intellectual disability syndromic and non-syndromic v0.1936 FDXR Zornitza Stark Marked gene: FDXR as ready
Intellectual disability syndromic and non-syndromic v0.1933 FGF14 Zornitza Stark reviewed gene: FGF14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 27, MIM# 609307; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1933 FANCG Zornitza Stark Marked gene: FANCG as ready
Intellectual disability syndromic and non-syndromic v0.1932 FANCB Zornitza Stark Marked gene: FANCB as ready
Intellectual disability syndromic and non-syndromic v0.1928 FANCD2 Zornitza Stark edited their review of gene: FANCD2: Added comment: Clinical presentation is typically with congenital abnormalities/BMF. Only ~10% have ID as part of the phenotype.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.1927 ERCC4 Zornitza Stark changed review comment from: Intellect normal in xeroderma pigmentosum; mild learning difficulties described in XFE progressed syndrome.; to: Intellect normal in xeroderma pigmentosum; mild learning difficulties described in XFE progeroid syndrome.
Intellectual disability syndromic and non-syndromic v0.1927 EPB41L1 Zornitza Stark Marked gene: EPB41L1 as ready
Intellectual disability syndromic and non-syndromic v0.1927 EPB41L1 Zornitza Stark Phenotypes for gene: EPB41L1 were changed from to Mental retardation, autosomal dominant 11, MIM# 614257
Intellectual disability syndromic and non-syndromic v0.1923 EPB41L1 Zornitza Stark reviewed gene: EPB41L1: Rating: RED; Mode of pathogenicity: None; Publications: 21376300, 26539891, 25961944; Phenotypes: Mental retardation, autosomal dominant 11 614257; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1923 EMG1 Zornitza Stark Marked gene: EMG1 as ready
Intellectual disability syndromic and non-syndromic v0.1921 EMC1 Zornitza Stark Marked gene: EMC1 as ready
Intellectual disability syndromic and non-syndromic v0.1920 EMC1 Zornitza Stark gene: EMC1 was added
gene: EMC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: EMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMC1 were set to 26942288; 29271071
Phenotypes for gene: EMC1 were set to Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM# 616875
Review for gene: EMC1 was set to GREEN
gene: EMC1 was marked as current diagnostic
Added comment: Four unrelated families with bi-allelic variants in this gene reported. Single individual with heterozygous variant: insufficient evidence at present for mono allelic variants causing disease.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1919 EFNB1 Zornitza Stark Marked gene: EFNB1 as ready
Intellectual disability syndromic and non-syndromic v0.1916 ATAD3A Zornitza Stark Marked gene: ATAD3A as ready
Intellectual disability syndromic and non-syndromic v0.1916 ATAD3A Zornitza Stark Phenotypes for gene: ATAD3A were changed from to Harel-Yoon syndrome, MIM# 617183
Intellectual disability syndromic and non-syndromic v0.1913 ATAD3A Zornitza Stark reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27640307, 32004445; Phenotypes: Harel-Yoon syndrome, MIM# 617183; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1913 DPM3 Zornitza Stark Marked gene: DPM3 as ready
Intellectual disability syndromic and non-syndromic v0.1910 DPM3 Zornitza Stark Phenotypes for gene: DPM3 were changed from to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 612937
Intellectual disability syndromic and non-syndromic v0.1908 DPM3 Zornitza Stark reviewed gene: DPM3: Rating: RED; Mode of pathogenicity: None; Publications: 19576565, 28803818, 30931530, 31469168; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15 612937; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1908 DPM2 Zornitza Stark Marked gene: DPM2 as ready
Intellectual disability syndromic and non-syndromic v0.1904 DNAJC3 Zornitza Stark Marked gene: DNAJC3 as ready
Intellectual disability syndromic and non-syndromic v0.1904 DNAJC3 Zornitza Stark Phenotypes for gene: DNAJC3 were changed from to Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, MIM# 616192
Intellectual disability syndromic and non-syndromic v0.1900 DNAJC3 Zornitza Stark reviewed gene: DNAJC3: Rating: RED; Mode of pathogenicity: None; Publications: 25466870, 28940199; Phenotypes: Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, MIM# 616192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1900 DLG4 Zornitza Stark Marked gene: DLG4 as ready
Intellectual disability syndromic and non-syndromic v0.1900 DLG4 Zornitza Stark Phenotypes for gene: DLG4 were changed from to Intellectual disability; Marfanoid habitus
Intellectual disability syndromic and non-syndromic v0.1896 DLG4 Zornitza Stark edited their review of gene: DLG4: Added comment: Four unrelated individuals reported.; Changed rating: GREEN; Changed publications: 27479843, 25123844, 19617690, 29460436, 23020937, 28135719; Changed phenotypes: Intellectual disability, Marfanoid habitus; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Set current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.1895 DLAT Zornitza Stark edited their review of gene: DLAT: Added comment: Only two families with ID reported; third individual had paroxysmal dyskinesia.; Changed rating: AMBER; Changed publications: 16049940, 29093066
Intellectual disability syndromic and non-syndromic v0.1895 DIP2B Zornitza Stark Marked gene: DIP2B as ready
Intellectual disability syndromic and non-syndromic v0.1895 DIP2B Zornitza Stark Phenotypes for gene: DIP2B were changed from to Mental retardation, FRA12A type, MIM# 136630
Intellectual disability syndromic and non-syndromic v0.1893 DIP2B Zornitza Stark Mode of pathogenicity for gene: DIP2B 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 v0.1889 DIP2B Zornitza Stark reviewed gene: DIP2B: Rating: AMBER; 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: 17236128; Phenotypes: Mental retardation, FRA12A type, MIM# 136630; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1889 DENND5A Zornitza Stark Marked gene: DENND5A as ready
Intellectual disability syndromic and non-syndromic v0.1888 DENND5A Zornitza Stark gene: DENND5A was added
gene: DENND5A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: DENND5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DENND5A were set to 27431290; 27866705
Phenotypes for gene: DENND5A were set to Epileptic encephalopathy, early infantile, 49, MIM# 617281
Review for gene: DENND5A was set to GREEN
Added comment: Four unrelated families, ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1887 DCPS Zornitza Stark Marked gene: DCPS as ready
Intellectual disability syndromic and non-syndromic v0.1886 DCPS Zornitza Stark gene: DCPS was added
gene: DCPS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: DCPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCPS were set to 25701870; 30289615; 25712129
Phenotypes for gene: DCPS were set to Al-Raqad syndrome, MIM#616459
Review for gene: DCPS was set to GREEN
gene: DCPS was marked as current diagnostic
Added comment: 7 individuals from 3 families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1885 CWF19L1 Zornitza Stark Marked gene: CWF19L1 as ready
Intellectual disability syndromic and non-syndromic v0.1884 CWF19L1 Zornitza Stark gene: CWF19L1 was added
gene: CWF19L1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CWF19L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWF19L1 were set to 25361784; 15981765; 26197978; 27016154; 30167849
Phenotypes for gene: CWF19L1 were set to Spinocerebellar ataxia, autosomal recessive 17, MIM#616127; intellectual disability, developmental delay
Review for gene: CWF19L1 was set to GREEN
gene: CWF19L1 was marked as current diagnostic
Added comment: Three unrelated families reported, ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1883 CUX1 Zornitza Stark Marked gene: CUX1 as ready
Intellectual disability syndromic and non-syndromic v0.1882 CUX1 Zornitza Stark gene: CUX1 was added
gene: CUX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CUX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUX1 were set to 25059644; 20510857; 30014507
Phenotypes for gene: CUX1 were set to Global developmental delay with or without impaired intellectual development, MIM#618330
Review for gene: CUX1 was set to GREEN
gene: CUX1 was marked as current diagnostic
Added comment: Nine individuals from 7 families reported. Three individuals had normal intelligence at school age despite significant early developmental delay.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1881 CRBN Zornitza Stark Marked gene: CRBN as ready
Intellectual disability syndromic and non-syndromic v0.1881 CRBN Zornitza Stark Phenotypes for gene: CRBN were changed from to Mental retardation, autosomal recessive 2, MIM# 607417
Intellectual disability syndromic and non-syndromic v0.1878 CRBN Zornitza Stark reviewed gene: CRBN: Rating: AMBER; Mode of pathogenicity: None; Publications: 15557513, 28143899; Phenotypes: Mental retardation, autosomal recessive 2, MIM# 607417; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.1876 COQ2 Zornitza Stark edited their review of gene: COQ2: Added comment: On further review of the literature, there is poor documentation of intellectual disability as such in the molecularly confirmed cases. Presentation is much more commonly with renal or multi-system disease.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.1876 COL1A2 Zornitza Stark Marked gene: COL1A2 as ready
Intellectual disability syndromic and non-syndromic v0.1876 COLEC10 Zornitza Stark Marked gene: COLEC10 as ready
Intellectual disability syndromic and non-syndromic v0.1872 COL1A2 Zornitza Stark Phenotypes for gene: COL1A2 were changed from to Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821; Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320; Osteogenesis imperfecta, type II, MIM# 166210; Osteogenesis imperfecta, type III, MIM# 259420; Osteogenesis imperfecta, type IV, MIM# 166220
Intellectual disability syndromic and non-syndromic v0.1869 COL1A2 Zornitza Stark reviewed gene: COL1A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, arthrochalasia type, 2, MIM# 617821, Ehlers-Danlos syndrome, cardiac valvular type, MIM# 225320, Osteogenesis imperfecta, type II, MIM# 166210, Osteogenesis imperfecta, type III, MIM# 259420, Osteogenesis imperfecta, type IV, MIM# 166220; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1869 COA3 Zornitza Stark Marked gene: COA3 as ready
Intellectual disability syndromic and non-syndromic v0.1868 CNTN3 Zornitza Stark Marked gene: CNTN3 as ready
Intellectual disability syndromic and non-syndromic v0.1864 CLPP Zornitza Stark Marked gene: CLPP as ready
Intellectual disability syndromic and non-syndromic v0.1860 CHRNA4 Zornitza Stark Marked gene: CHRNA4 as ready
Intellectual disability syndromic and non-syndromic v0.1856 CHD1 Zornitza Stark edited their review of gene: CHD1: Added comment: Possible dominant negative mechanism: reported variants are missense, an individual with a deletion did not have a neurological phenotype.; Changed mode of pathogenicity: Other
Intellectual disability syndromic and non-syndromic v0.1856 CEP104 Zornitza Stark Marked gene: CEP104 as ready
Intellectual disability syndromic and non-syndromic v0.1855 CEP104 Zornitza Stark gene: CEP104 was added
gene: CEP104 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CEP104 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP104 were set to 26477546
Phenotypes for gene: CEP104 were set to Joubert syndrome 25, MIM# 616781
Review for gene: CEP104 was set to GREEN
Added comment: Three unrelated individuals reported, ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1854 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Intellectual disability syndromic and non-syndromic v0.1851 CDK5R1 Zornitza Stark Marked gene: CDK5R1 as ready
Intellectual disability syndromic and non-syndromic v0.1847 CCDC88A Zornitza Stark Marked gene: CCDC88A as ready
Intellectual disability syndromic and non-syndromic v0.1844 CARS2 Zornitza Stark Marked gene: CARS2 as ready
Intellectual disability syndromic and non-syndromic v0.1844 CARS2 Zornitza Stark Gene: cars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1844 CARS2 Zornitza Stark Classified gene: CARS2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.1844 CARS2 Zornitza Stark Gene: cars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1843 CARS2 Zornitza Stark gene: CARS2 was added
gene: CARS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARS2 were set to 30139652; 25787132
Phenotypes for gene: CARS2 were set to Combined oxidative phosphorylation deficiency 27, MIM#616672
Review for gene: CARS2 was set to GREEN
Added comment: Three unrelated individuals described with this mitochondrial disorder, ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1842 CANT1 Zornitza Stark Marked gene: CANT1 as ready
Intellectual disability syndromic and non-syndromic v0.1839 CA5A Zornitza Stark Marked gene: CA5A as ready
Intellectual disability syndromic and non-syndromic v0.1839 CA5A Zornitza Stark Phenotypes for gene: CA5A were changed from to Hyperammonemia due to carbonic anhydrase VA deficiency, MIM# 615751
Intellectual disability syndromic and non-syndromic v0.1837 KIF1A Zornitza Stark Marked gene: KIF1A as ready
Intellectual disability syndromic and non-syndromic v0.1837 KIF1A Zornitza Stark Added comment: Comment when marking as ready: Monoallelic variants associated with ID; bi-allelic variants associated with neuropathy/spastic paraplegia phenotypes.
Intellectual disability syndromic and non-syndromic v0.1837 KIF1A Zornitza Stark Phenotypes for gene: KIF1A were changed from to Mental retardation, autosomal dominant 9, MIM#614255
Intellectual disability syndromic and non-syndromic v0.1833 ACSL4 Zornitza Stark Marked gene: ACSL4 as ready
Intellectual disability syndromic and non-syndromic v0.1833 ACSL4 Zornitza Stark Added comment: Comment when marking as ready: At least three unrelated individuals reported.
Intellectual disability syndromic and non-syndromic v0.1833 ACSL4 Zornitza Stark Phenotypes for gene: ACSL4 were changed from to Mental retardation, X-linked 63, MIM# 300387 XLD
Intellectual disability syndromic and non-syndromic v0.1830 CAMTA1 Zornitza Stark Marked gene: CAMTA1 as ready
Intellectual disability syndromic and non-syndromic v0.1830 CAMTA1 Zornitza Stark Phenotypes for gene: CAMTA1 were changed from to Cerebellar ataxia, nonprogressive, with mental retardation (614756 AD)
Intellectual disability syndromic and non-syndromic v0.1829 HUWE1 Zornitza Stark Marked gene: HUWE1 as ready
Intellectual disability syndromic and non-syndromic v0.1828 HUWE1 Zornitza Stark Phenotypes for gene: HUWE1 were changed from to Mental retardation, X-linked syndromic, Turner type
Intellectual disability syndromic and non-syndromic v0.1826 HUWE1 Zornitza Stark reviewed gene: HUWE1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Turner type; 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 v0.1826 LAMA2 Zornitza Stark Marked gene: LAMA2 as ready
Intellectual disability syndromic and non-syndromic v0.1826 LAMA2 Zornitza Stark Phenotypes for gene: LAMA2 were changed from to Muscular dystrophy, congenital, merosin deficient or partially deficient, 607855; Muscular dystrophy, limb-girdle, autosomal recessive 23, MIM#618138; LAMA2-related muscular dystrophy (suggested by PMID: 30055037)
Intellectual disability syndromic and non-syndromic v0.1823 EBP Zornitza Stark Marked gene: EBP as ready
Intellectual disability syndromic and non-syndromic v0.1823 EBP Zornitza Stark Added comment: Comment when marking as ready: CDP lethal in males (unless mosaic) and females generally have normal intellectual development. Hypomorphic variants in males result in MEND, which has ID as a feature (carrier females for these variants generally asymptomatic).
Intellectual disability syndromic and non-syndromic v0.1821 ALDH3A2 Zornitza Stark Marked gene: ALDH3A2 as ready
Intellectual disability syndromic and non-syndromic v0.1821 ALDH3A2 Zornitza Stark Phenotypes for gene: ALDH3A2 were changed from to Sjogren-Larsson syndrome MIM#270200; spasticity; ichthyosis; intellectual disability
Intellectual disability syndromic and non-syndromic v0.1818 ALDH3A2 Zornitza Stark reviewed gene: ALDH3A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31273323; Phenotypes: Sjogren-Larsson syndrome MIM#270200, spasticity, ichthyosis, intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1818 ABHD5 Zornitza Stark Marked gene: ABHD5 as ready
Intellectual disability syndromic and non-syndromic v0.1818 ABHD5 Zornitza Stark Phenotypes for gene: ABHD5 were changed from to Chanarin-Dorfman syndrome MIM#275630; neutral lipid storage disease with ichthyosis; non-bullous congenital ichthyosiform erythroderma
Intellectual disability syndromic and non-syndromic v0.1815 ABHD5 Zornitza Stark reviewed gene: ABHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 30795549; Phenotypes: Chanarin-Dorfman syndrome MIM#275630, neutral lipid storage disease with ichthyosis, non-bullous congenital ichthyosiform erythroderma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1815 TUBGCP6 Zornitza Stark Marked gene: TUBGCP6 as ready
Intellectual disability syndromic and non-syndromic v0.1812 GNAS Zornitza Stark Marked gene: GNAS as ready
Intellectual disability syndromic and non-syndromic v0.1812 GNAS Zornitza Stark Phenotypes for gene: GNAS were changed from to Pseudohypoparathyroidism Ia (103580); Pseudohypoparathyroidism Ib (603233); Pseudohypoparathyroidism Ic (612462); Pseudopseudohypoparathyroidism (612463)
Intellectual disability syndromic and non-syndromic v0.1810 MYT1L Zornitza Stark Marked gene: MYT1L as ready
Intellectual disability syndromic and non-syndromic v0.1809 MYT1L Zornitza Stark Phenotypes for gene: MYT1L were changed from to Mental retardation, autosomal dominant 39, MIM# 616521
Intellectual disability syndromic and non-syndromic v0.1807 IRF2BPL Zornitza Stark Marked gene: IRF2BPL as ready
Intellectual disability syndromic and non-syndromic v0.1805 KIF1A Michelle Torres reviewed gene: KIF1A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 28970574, PMID: 22258533, PMID 31488895, PMID 31512412; Phenotypes: 1. Mental retardation, autosomal dominant 9 614255 AD, 2. Neuropathy, hereditary sensory, type IIC 614213 AR, 3. Spastic paraplegia 30, autosomal recessive 610357 AR, 4. Hereditary spastic paraplegia, AD (PMID 31488895), 5. Rett syndrome (typical) AD (PMID 31512412); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1805 ACSL4 Michelle Torres reviewed gene: ACSL4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:12525535; Phenotypes: 1. Mental retardation, X-linked 63 300387 XLD; 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 v0.1805 CAMTA1 Michelle Torres reviewed gene: CAMTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar ataxia, nonprogressive, with mental retardation (614756 AD); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1805 LAMA2 Michelle Torres reviewed gene: LAMA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30055037; Phenotypes: 1) Muscular dystrophy, congenital, merosin deficient or partially deficient, 607855 AR 2), Muscular dystrophy, limb-girdle, autosomal recessive 23, 618138 AR, 3 LAMA2-related muscular dystrophy (suggested by PMID: 30055037); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1804 PHF8 Zornitza Stark Marked gene: PHF8 as ready
Intellectual disability syndromic and non-syndromic v0.1803 PHF8 Zornitza Stark Phenotypes for gene: PHF8 were changed from to Mental retardation syndrome, X-linked, Siderius type, MIM#300263
Intellectual disability syndromic and non-syndromic v0.1801 PHF8 Zornitza Stark reviewed gene: PHF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17661819, 17594395, 16199551; Phenotypes: Mental retardation syndrome, X-linked, Siderius type, MIM#300263; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.1801 IARS Zornitza Stark Marked gene: IARS as ready
Intellectual disability syndromic and non-syndromic v0.1801 IARS Zornitza Stark Gene: iars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1801 IARS Zornitza Stark Phenotypes for gene: IARS were changed from to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093
Intellectual disability syndromic and non-syndromic v0.1800 IARS Zornitza Stark Publications for gene: IARS were set to
Intellectual disability syndromic and non-syndromic v0.1799 IARS Zornitza Stark Mode of inheritance for gene: IARS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1798 IARS Zornitza Stark reviewed gene: IARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27426735; Phenotypes: Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1798 SOX5 Zornitza Stark Marked gene: SOX5 as ready
Intellectual disability syndromic and non-syndromic v0.1798 SOX5 Zornitza Stark Added comment: Comment when marking as ready: Note many cases reported of intragenic deletion.
Intellectual disability syndromic and non-syndromic v0.1795 GNAS Michelle Torres reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29072892; Phenotypes: 1. ACTH-independent macronodular adrenal hyperplasia (219080) Somatic Mutations, 2. McCune-Albright syndrome, somatic, mosaic (174800), 3. Osseous heteroplasia, progressive (166350) AD, 4. Pituitary adenoma 3, multiple types, somatic (617686), 5. Pseudohypoparathyroidism Ia (103580) AD, 6. Pseudohypoparathyroidism Ib (603233) AD, 7. Pseudohypoparathyroidism Ic (612462) AD, 8. Pseudopseudohypoparathyroidism (612463) AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.1795 GNAS Michelle Torres reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29072892; Phenotypes: 1. ACTH-independent macronodular adrenal hyperplasia (219080) Somatic Mutations, 2. McCune-Albright syndrome, somatic, mosaic (174800), 3. Osseous heteroplasia, progressive (166350) AD, 4. Pituitary adenoma 3, multiple types, somatic (617686), 5. Pseudohypoparathyroidism Ia (103580) AD, 6. Pseudohypoparathyroidism Ib (603233) AD, 7. Pseudohypoparathyroidism Ic (612462) AD, 8. Pseudopseudohypoparathyroidism (612463) AD; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.1795 MYT1L Michelle Torres reviewed gene: MYT1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 39 616521 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1795 GNAO1 Zornitza Stark Marked gene: GNAO1 as ready
Intellectual disability syndromic and non-syndromic v0.1795 GNAO1 Zornitza Stark Phenotypes for gene: GNAO1 were changed from Epileptic encephalopathy, early infantile, 17; Neurodevelopmental disorder with involuntary movements to Epileptic encephalopathy, early infantile, 17; Neurodevelopmental disorder with involuntary movements
Intellectual disability syndromic and non-syndromic v0.1794 GNAO1 Zornitza Stark Phenotypes for gene: GNAO1 were changed from to Epileptic encephalopathy, early infantile, 17; Neurodevelopmental disorder with involuntary movements
Intellectual disability syndromic and non-syndromic v0.1790 GNAO1 Zornitza Stark reviewed gene: GNAO1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28747448, 30682224; Phenotypes: Epileptic encephalopathy, early infantile, 17, Neurodevelopmental disorder with involuntary movements; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1790 CAD Zornitza Stark Marked gene: CAD as ready
Intellectual disability syndromic and non-syndromic v0.1789 CAD Zornitza Stark gene: CAD was added
gene: CAD was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 25678555; 28007989; 30914295
Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50, MIM# MIM 616457
Review for gene: CAD was set to GREEN
gene: CAD was marked as current diagnostic
Added comment: Four unrelated families (two with same variant and Roma background, likely founder).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1788 CACNG2 Zornitza Stark Marked gene: CACNG2 as ready
Intellectual disability syndromic and non-syndromic v0.1787 CACNG2 Zornitza Stark Phenotypes for gene: CACNG2 were changed from to Mental retardation, autosomal dominant 10, MIM#614256
Intellectual disability syndromic and non-syndromic v0.1784 CACNG2 Zornitza Stark reviewed gene: CACNG2: Rating: RED; Mode of pathogenicity: None; Publications: 21376300; Phenotypes: Mental retardation, autosomal dominant 10, MIM#614256; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1784 PPM1D Zornitza Stark Marked gene: PPM1D as ready
Intellectual disability syndromic and non-syndromic v0.1780 CLCNKA Zornitza Stark edited their review of gene: CLCNKA: Added comment: Two families reported, and note digenic inheritance for Bartter postulated. PMID: 15044642 - Schlingmann et al 2004 - in a child with a child with renal salt wasting and deafness, they identified both a homozygous deletion of the CLCNKB gene and a homozygous trp80-to-cys mutation in the CLCNKA gene (W80C). PubMed: 18310267- Nozu et al 2008 - 2-year-old Japanese girl with a severe form of Bartter syndrome with sensorineural deafness. Parents were nonconsanguineous. They found 2 heterozygous mutations in the CLCNKA and CLCNKB genes on the paternal allele, and a 12-kb deletion involving portions of the CLCNKA and CLCNKB genes on the maternal allele. Neither parent was clinically affected.

ID has been described for Bartter, but since gene-disease association for Bartter itself is not well established, demote to Red.; Changed rating: RED
Intellectual disability syndromic and non-syndromic v0.1780 CACNA2D2 Zornitza Stark Marked gene: CACNA2D2 as ready
Intellectual disability syndromic and non-syndromic v0.1779 CACNA2D2 Zornitza Stark gene: CACNA2D2 was added
gene: CACNA2D2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CACNA2D2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA2D2 were set to 23339110; 24358150; 30410802; 29997391; 31402629; 11487633; 11756448; 4177347; 14660671; 15331424
Phenotypes for gene: CACNA2D2 were set to Cerebellar atrophy with seizures and variable developmental delay, MIM#618501
Review for gene: CACNA2D2 was set to GREEN
Added comment: Multiple affected individuals reported; DD/ID is variable but present in most.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1776 CA5A Zornitza Stark reviewed gene: CA5A: Rating: RED; Mode of pathogenicity: None; Publications: 26913920; Phenotypes: Hyperammonemia due to carbonic anhydrase VA deficiency, MIM# 615751; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1776 C8orf37 Zornitza Stark Marked gene: C8orf37 as ready
Intellectual disability syndromic and non-syndromic v0.1775 C8orf37 Zornitza Stark gene: C8orf37 was added
gene: C8orf37 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: C8orf37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C8orf37 were set to 26854863; 27008867
Phenotypes for gene: C8orf37 were set to Bardet-Biedl syndrome 21, MIM#617406
Review for gene: C8orf37 was set to AMBER
Added comment: Two unrelated individuals reported with BBS; note gene has an association with retinal ciliopathies.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1774 C2CD3 Zornitza Stark Marked gene: C2CD3 as ready
Intellectual disability syndromic and non-syndromic v0.1771 BSND Zornitza Stark edited their review of gene: BSND: Added comment: Downgrade to Amber after review against GEL panel; ID not a consistent/predominant feature of Bartter syndrome.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.1769 BIN1 Zornitza Stark Marked gene: BIN1 as ready
Intellectual disability syndromic and non-syndromic v0.1769 BIN1 Zornitza Stark Phenotypes for gene: BIN1 were changed from Centronuclear myopathy 2, MIM# 255200 to Centronuclear myopathy 2, MIM# 255200
Intellectual disability syndromic and non-syndromic v0.1768 BIN1 Zornitza Stark Phenotypes for gene: BIN1 were changed from to Centronuclear myopathy 2, MIM# 255200
Intellectual disability syndromic and non-syndromic v0.1766 BIN1 Zornitza Stark reviewed gene: BIN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Centronuclear myopathy 2, MIM# 255200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1766 ATP6V1A Zornitza Stark Marked gene: ATP6V1A as ready
Intellectual disability syndromic and non-syndromic v0.1764 ATP6V1A Zornitza Stark gene: ATP6V1A was added
gene: ATP6V1A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: ATP6V1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ATP6V1A were set to 29668857; 28065471
Phenotypes for gene: ATP6V1A were set to Epileptic encephalopathy, infantile or early childhood, 3 618012; Cutis laxa, autosomal recessive, type IID 617403
Mode of pathogenicity for gene: ATP6V1A was set to Other
Review for gene: ATP6V1A was set to GREEN
gene: ATP6V1A was marked as current diagnostic
Added comment: Both mono-allelic and bi-allelic variants associated with ID, evidence for both LoF and GoF for the mono-allelic variants.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1763 ATP1A2 Zornitza Stark Marked gene: ATP1A2 as ready
Intellectual disability syndromic and non-syndromic v0.1760 FBXW11 Alison Yeung Marked gene: FBXW11 as ready
Intellectual disability syndromic and non-syndromic v0.1759 FBXW11 Alison Yeung gene: FBXW11 was added
gene: FBXW11 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FBXW11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FBXW11 were set to PMID: 31402090
Phenotypes for gene: FBXW11 were set to Intellectual disability; developmental eye anomalies; digital anomalies
Review for gene: FBXW11 was set to GREEN
gene: FBXW11 was marked as current diagnostic
Added comment: Reported in >3 unrelated individuals
Functional studies in Zebrafish
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1758 MAB21L1 Zornitza Stark Marked gene: MAB21L1 as ready
Intellectual disability syndromic and non-syndromic v0.1756 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Rare Disease
Intellectual disability syndromic and non-syndromic v0.1755 ASMT Zornitza Stark Marked gene: ASMT as ready
Intellectual disability syndromic and non-syndromic v0.1752 MAB21L1 Sue White gene: MAB21L1 was added
gene: MAB21L1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAB21L1 were set to 30487245
Phenotypes for gene: MAB21L1 were set to Cerebellar, ocular, craniofacial, and genital syndrome MIM#618479
Penetrance for gene: MAB21L1 were set to Complete
Review for gene: MAB21L1 was set to GREEN
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1751 ARHGEF6 Zornitza Stark Phenotypes for gene: ARHGEF6 were changed from MENTAL RETARDATION X-LINKED TYPE 46 to MENTAL RETARDATION X-LINKED TYPE 46
Intellectual disability syndromic and non-syndromic v0.1751 ARHGEF6 Zornitza Stark Marked gene: ARHGEF6 as ready
Intellectual disability syndromic and non-syndromic v0.1751 ARHGEF6 Zornitza Stark Gene: arhgef6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.1751 ARHGEF6 Zornitza Stark Phenotypes for gene: ARHGEF6 were changed from to MENTAL RETARDATION X-LINKED TYPE 46
Intellectual disability syndromic and non-syndromic v0.1750 ARHGEF6 Zornitza Stark Publications for gene: ARHGEF6 were set to 11017088
Intellectual disability syndromic and non-syndromic v0.1750 ARHGEF6 Zornitza Stark Publications for gene: ARHGEF6 were set to
Intellectual disability syndromic and non-syndromic v0.1749 AR Zornitza Stark Marked gene: AR as ready
Intellectual disability syndromic and non-syndromic v0.1749 AR Zornitza Stark Gene: ar has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.1749 AR Zornitza Stark Phenotypes for gene: AR were changed from to Spinal and bulbar muscular atrophy of Kennedy, MIM# 313200
Intellectual disability syndromic and non-syndromic v0.1749 ARHGEF6 Zornitza Stark Classified gene: ARHGEF6 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.1749 ARHGEF6 Zornitza Stark Gene: arhgef6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.1748 ARHGEF6 Zornitza Stark Mode of inheritance for gene: ARHGEF6 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.1747 ARHGEF6 Zornitza Stark Classified gene: ARHGEF6 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.1747 ARHGEF6 Zornitza Stark Gene: arhgef6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.1746 ARHGEF6 Zornitza Stark reviewed gene: ARHGEF6: Rating: RED; Mode of pathogenicity: None; Publications: 11017088; Phenotypes: MENTAL RETARDATION X-LINKED TYPE 46; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.1746 AR Zornitza Stark Mode of inheritance for gene: AR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.1746 AR Zornitza Stark Classified gene: AR as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.1746 AR Zornitza Stark Gene: ar has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.1745 AR Zornitza Stark reviewed gene: AR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal and bulbar muscular atrophy of Kennedy, MIM# 313200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.1745 ANK3 Zornitza Stark Marked gene: ANK3 as ready
Intellectual disability syndromic and non-syndromic v0.1744 ANK3 Zornitza Stark Phenotypes for gene: ANK3 were changed from to Mental retardation, autosomal recessive, 37 615493
Intellectual disability syndromic and non-syndromic v0.1742 ANK3 Zornitza Stark reviewed gene: ANK3: Rating: RED; Mode of pathogenicity: None; Publications: 23390136, 28687526; Phenotypes: Mental retardation, autosomal recessive, 37 615493; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1742 ALX4 Zornitza Stark Marked gene: ALX4 as ready
Intellectual disability syndromic and non-syndromic v0.1737 ALG2 Zornitza Stark Marked gene: ALG2 as ready
Intellectual disability syndromic and non-syndromic v0.1737 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Congenital disorder of glycosylation, type Ii, MIM# 607906 to Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Congenital disorder of glycosylation, type Ii, MIM# 607906
Intellectual disability syndromic and non-syndromic v0.1736 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from to Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Congenital disorder of glycosylation, type Ii, MIM# 607906
Intellectual disability syndromic and non-syndromic v0.1733 ALG2 Zornitza Stark reviewed gene: ALG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228, Congenital disorder of glycosylation, type Ii, MIM# 607906; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1733 CACNA1D Zornitza Stark Phenotypes for gene: CACNA1D were changed from Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474; intellectual disability; autism; epilepsy to Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474; intellectual disability; autism; epilepsy
Intellectual disability syndromic and non-syndromic v0.1733 CACNA1D Zornitza Stark Marked gene: CACNA1D as ready
Intellectual disability syndromic and non-syndromic v0.1733 CACNA1D Zornitza Stark Phenotypes for gene: CACNA1D were changed from to Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474; intellectual disability; autism; epilepsy
Intellectual disability syndromic and non-syndromic v0.1731 CACNA1D Zornitza Stark reviewed gene: CACNA1D: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31921405, 28472301, 25620733; Phenotypes: Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474, intellectual disability, autism, epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1730 ANKRD11 Zornitza Stark Marked gene: ANKRD11 as ready
Intellectual disability syndromic and non-syndromic v0.1728 CTBP1 Zornitza Stark Marked gene: CTBP1 as ready
Intellectual disability syndromic and non-syndromic v0.1727 CTBP1 Sebastian Lunke gene: CTBP1 was added
gene: CTBP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTBP1 were set to 27094857; 28955726; 31041561
Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, 617915
gene: CTBP1 was marked as current diagnostic
Added comment: From GEL: There are 12 individuals reported from 3 papers (2 papers from the same group). All 12 individuals have the same heterozygous missense variant (R331W in NM_001012614.1; R342W in NM_001328.2). It is a de novo variant in all cases except one where it's inherited from a somatic parent. The phenotype of all 12 is summarised in Table 1 of PMID:31041561. Global DD is a consistent feature (varying severity). ID is recorded in several patients. Developmental motor regression recorded in 4 patients (2 of which also had cognitive regression). Authors note that healthy individuals with heterozygous LOF alleles have been reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1727 CTBP1 Sebastian Lunke gene: CTBP1 was added
gene: CTBP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTBP1 were set to 27094857; 28955726; 31041561
Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, 617915
gene: CTBP1 was marked as current diagnostic
Added comment: From GEL: There are 12 individuals reported from 3 papers (2 papers from the same group). All 12 individuals have the same heterozygous missense variant (R331W in NM_001012614.1; R342W in NM_001328.2). It is a de novo variant in all cases except one where it's inherited from a somatic parent. The phenotype of all 12 is summarised in Table 1 of PMID:31041561. Global DD is a consistent feature (varying severity). ID is recorded in several patients. Developmental motor regression recorded in 4 patients (2 of which also had cognitive regression). Authors note that healthy individuals with heterozygous LOF alleles have been reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1725 AGO1 Zornitza Stark Marked gene: AGO1 as ready
Intellectual disability syndromic and non-syndromic v0.1724 AGO1 Zornitza Stark gene: AGO1 was added
gene: AGO1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: AGO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGO1 were set to 30213762; 22495306; 23020937; 25363768; 25356899; 27620904; 29346770; 28135719
Phenotypes for gene: AGO1 were set to Intellectual disability; autism
Review for gene: AGO1 was set to GREEN
Added comment: Multiple individuals reported with de novo variants in this gene, most as part of large ID cohorts so phenotypic information is scarce; however, given large number I have rated as Green.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1723 CNOT2 Sebastian Lunke Marked gene: CNOT2 as ready
Intellectual disability syndromic and non-syndromic v0.1722 CNOT2 Sebastian Lunke gene: CNOT2 was added
gene: CNOT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CNOT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT2 were set to 31512373; 31145527; 28135719
Phenotypes for gene: CNOT2 were set to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies 618608
Review for gene: CNOT2 was set to GREEN
gene: CNOT2 was marked as current diagnostic
Added comment: From GEL: Three independent patients with non-sense or intra-genic deletions
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1721 AGL Zornitza Stark Marked gene: AGL as ready
Intellectual disability syndromic and non-syndromic v0.1719 CNOT1 Sebastian Lunke Marked gene: CNOT1 as ready
Intellectual disability syndromic and non-syndromic v0.1718 CNOT1 Sebastian Lunke gene: CNOT1 was added
gene: CNOT1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CNOT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT1 were set to 31006510; 21679367; 31006513
Phenotypes for gene: CNOT1 were set to Holoprosencephaly 12, with or without pancreatic agenesis 618500
Review for gene: CNOT1 was set to GREEN
gene: CNOT1 was marked as current diagnostic
Added comment: From GEL: More than three independent families previously described
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1717 ACAT1 Zornitza Stark Marked gene: ACAT1 as ready
Intellectual disability syndromic and non-syndromic v0.1717 CCDC88C Sebastian Lunke Phenotypes for gene: CCDC88C were changed from Spinocerebellar ataxia 40, MIM#616053 to Hydrocephalus, nonsyndromic, autosomal recessive 236600 AR
Intellectual disability syndromic and non-syndromic v0.1714 CCDC88C Sebastian Lunke reviewed gene: CCDC88C: Rating: GREEN; Mode of pathogenicity: None; Publications: 23042809, 21031079; Phenotypes: Hydrocephalus, nonsyndromic, autosomal recessive 236600 AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.1712 CCDC47 Sebastian Lunke Marked gene: CCDC47 as ready
Intellectual disability syndromic and non-syndromic v0.1712 CCDC47 Sebastian Lunke gene: CCDC47 was added
gene: CCDC47 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CCDC47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC47 were set to 30401460
Phenotypes for gene: CCDC47 were set to Trichohepatoneurodevelopmental syndrome, 618268
Review for gene: CCDC47 was set to GREEN
gene: CCDC47 was marked as current diagnostic
Added comment: From GEL: Morimoto el al. (PMID: 30401460) report on 4 individuals from 4 unrelated families with biallelic LoF variants in CCDC47. The phenotype consisted of abnormal (woolly) hair, liver dysfunction, common facial features as well as DD/ID.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1708 ACADSB Zornitza Stark Marked gene: ACADSB as ready
Intellectual disability syndromic and non-syndromic v0.1708 ACAT1 Zornitza Stark commented on gene: ACAT1: Primarily manifests as metabolic decompensation, DD/ID reported in a few individuals, mostly normal cognition.
Intellectual disability syndromic and non-syndromic v0.1704 CLIC2 Zornitza Stark Marked gene: CLIC2 as ready
Intellectual disability syndromic and non-syndromic v0.1704 CLIC2 Zornitza Stark Phenotypes for gene: CLIC2 were changed from to Mental retardation, X-linked, syndromic 32, 300886
Intellectual disability syndromic and non-syndromic v0.1702 CLIC2 Zornitza Stark reviewed gene: CLIC2: Rating: RED; Mode of pathogenicity: None; Publications: 22814392, 25927380; Phenotypes: Mental retardation, X-linked, syndromic 32, 300886; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.1702 SLC6A9 Zornitza Stark Marked gene: SLC6A9 as ready
Intellectual disability syndromic and non-syndromic v0.1699 DHFR Zornitza Stark Marked gene: DHFR as ready
Intellectual disability syndromic and non-syndromic v0.1695 SLC39A8 Zornitza Stark Marked gene: SLC39A8 as ready
Intellectual disability syndromic and non-syndromic v0.1693 PIGS Zornitza Stark Marked gene: PIGS as ready
Intellectual disability syndromic and non-syndromic v0.1691 FUK Zornitza Stark Marked gene: FUK as ready
Intellectual disability syndromic and non-syndromic v0.1689 ZNF142 Zornitza Stark Marked gene: ZNF142 as ready
Intellectual disability syndromic and non-syndromic v0.1688 ZNF142 Zornitza Stark gene: ZNF142 was added
gene: ZNF142 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: ZNF142 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF142 were set to 31036918
Phenotypes for gene: ZNF142 were set to Neurodevelopmental disorder with impaired speech and hyperkinetic movements, MIM#618425
Review for gene: ZNF142 was set to GREEN
gene: ZNF142 was marked as current diagnostic
Added comment: 7 individuals from 4 unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1687 WARS2 Zornitza Stark Classified gene: WARS2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.1687 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1686 WARS2 Zornitza Stark gene: WARS2 was added
gene: WARS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS2 were set to 29783990; 28236339; 29120065; 28650581; 28905505
Phenotypes for gene: WARS2 were set to Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM#617710
Review for gene: WARS2 was set to GREEN
gene: WARS2 was marked as current diagnostic
Added comment: 7 unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1685 VPS11 Zornitza Stark Marked gene: VPS11 as ready
Intellectual disability syndromic and non-syndromic v0.1684 VPS11 Zornitza Stark gene: VPS11 was added
gene: VPS11 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: VPS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS11 were set to 27120463; 26307567; 27473128
Phenotypes for gene: VPS11 were set to Leukodystrophy, hypomyelinating, 12, MIM#616683
Review for gene: VPS11 was set to GREEN
Added comment: ID, (variable) acquired microcephaly with hypomyelination; seizures in several reported individuals. 13 individuals from 7 Ashkenazi Jewish families, homozygous for a founder mutation (NM_021729.5:c.2536T>G or p.Cys846Gly); a different variant (p.Leu387_Gly395del) reported in a consanguineous family.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1682 TRAPPC12 Zornitza Stark Marked gene: TRAPPC12 as ready
Intellectual disability syndromic and non-syndromic v0.1682 TRAPPC12 Zornitza Stark Added comment: Comment when marking as ready: Additional unpublished case reported by GEL PanelApp.
Intellectual disability syndromic and non-syndromic v0.1681 TRAPPC12 Zornitza Stark Phenotypes for gene: TRAPPC12 were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM#617669
Intellectual disability syndromic and non-syndromic v0.1679 TRAPPC12 Zornitza Stark reviewed gene: TRAPPC12: Rating: AMBER; Mode of pathogenicity: None; Publications: 28777934; Phenotypes: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM#617669; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1679 SLC1A4 Zornitza Stark Marked gene: SLC1A4 as ready
Intellectual disability syndromic and non-syndromic v0.1677 SLC1A4 Zornitza Stark gene: SLC1A4 was added
gene: SLC1A4 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SLC1A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC1A4 were set to 29989513; 27193218; 26138499; 26041762; 25930971
Phenotypes for gene: SLC1A4 were set to Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657
Review for gene: SLC1A4 was set to GREEN
gene: SLC1A4 was marked as current diagnostic
Added comment: Multiple affected individuals reported in the literature, seizures/EE are part of the phenotype. While initial reports identified a recurrent missense variant in individuals of Ashkenazi Jewish ancestry, there have been more recent reports of individuals from other ethnic backgrounds with different variants
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1676 NBEA Zornitza Stark Marked gene: NBEA as ready
Intellectual disability syndromic and non-syndromic v0.1675 NBEA Zornitza Stark gene: NBEA was added
gene: NBEA was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: NBEA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NBEA were set to 30269351; 28554332; 12746398; 12826745; 11450821; 3377648; 23277425; 22109531; 23153818
Phenotypes for gene: NBEA were set to Intellectual disability; Seizures
Review for gene: NBEA was set to GREEN
gene: NBEA was marked as current diagnostic
Added comment: 24 de novo variants reported in individuals with a neurodevelopmental disorder.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1674 MACF1 Zornitza Stark Marked gene: MACF1 as ready
Intellectual disability syndromic and non-syndromic v0.1673 MACF1 Zornitza Stark gene: MACF1 was added
gene: MACF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MACF1 were set to 30471716
Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation, MIM# 618325
Mode of pathogenicity for gene: MACF1 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: MACF1 was set to GREEN
Added comment: Nine individuals (including a pair of twins) reported with de novo, likely GoF variants in this gene.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1671 NLGN4X Zornitza Stark Marked gene: NLGN4X as ready
Intellectual disability syndromic and non-syndromic v0.1671 NLGN4X Zornitza Stark Phenotypes for gene: NLGN4X were changed from to Mental retardation, X-linked, MIM# 300495
Intellectual disability syndromic and non-syndromic v0.1667 NLGN4X Zornitza Stark reviewed gene: NLGN4X: Rating: RED; Mode of pathogenicity: None; Publications: 12669065, 18231125, 10071191, 29428674; Phenotypes: Mental retardation, X-linked, MIM# 300495; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.1667 KATNB1 Zornitza Stark Marked gene: KATNB1 as ready
Intellectual disability syndromic and non-syndromic v0.1666 KATNB1 Zornitza Stark gene: KATNB1 was added
gene: KATNB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: KATNB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KATNB1 were set to 25521378; 25521379; 26640080
Phenotypes for gene: KATNB1 were set to Lissencephaly 6, with microcephaly, MIM# 616212
Review for gene: KATNB1 was set to GREEN
Added comment: At least 9 families reported with bi-allelic variants in this gene.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1665 GNB5 Zornitza Stark Marked gene: GNB5 as ready
Intellectual disability syndromic and non-syndromic v0.1664 GNB5 Zornitza Stark gene: GNB5 was added
gene: GNB5 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: GNB5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNB5 were set to 27523599; 27677260; 28697420; 29368331
Phenotypes for gene: GNB5 were set to Intellectual developmental disorder with cardiac arrhythmia, 617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182; Early infantile epileptic encephalopathy (EIEE)
Review for gene: GNB5 was set to GREEN
gene: GNB5 was marked as current diagnostic
Added comment: Multiple affected individuals reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1663 FAR1 Zornitza Stark Marked gene: FAR1 as ready
Intellectual disability syndromic and non-syndromic v0.1663 FAR1 Zornitza Stark Gene: far1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.1663 FAR1 Zornitza Stark Phenotypes for gene: FAR1 were changed from to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154
Intellectual disability syndromic and non-syndromic v0.1663 FAR1 Zornitza Stark Publications for gene: FAR1 were set to
Intellectual disability syndromic and non-syndromic v0.1662 FAR1 Zornitza Stark Mode of inheritance for gene: FAR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1661 FAR1 Zornitza Stark Mode of inheritance for gene: FAR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1660 FAR1 Zornitza Stark Classified gene: FAR1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.1660 FAR1 Zornitza Stark Gene: far1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.1659 FAR1 Zornitza Stark reviewed gene: FAR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 25439727; Phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1659 GOT2 Zornitza Stark Marked gene: GOT2 as ready
Intellectual disability syndromic and non-syndromic v0.1658 GOT2 Zornitza Stark gene: GOT2 was added
gene: GOT2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GOT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GOT2 were set to 31422819
Phenotypes for gene: GOT2 were set to Epileptic encephalopathy, early infantile, 82, MIM# 618721
Review for gene: GOT2 was set to GREEN
Added comment: Four individuals from three unrelated families reported, EE/DD. Treatment with pyridoxine and serine ameliorated the phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1657 RAB11A Zornitza Stark Marked gene: RAB11A as ready
Intellectual disability syndromic and non-syndromic v0.1656 RAB11A Zornitza Stark gene: RAB11A was added
gene: RAB11A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAB11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB11A were set to 29100083
Phenotypes for gene: RAB11A were set to Intellectual disability; seizures
Review for gene: RAB11A was set to AMBER
Added comment: Five individuals reported with DNMs and neurodevelopmental phenotypes as part of this paper; however, clinical details are sparse. Emerging gene, phenotype not yet clearly delineated.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1655 DHPS Zornitza Stark Marked gene: DHPS as ready
Intellectual disability syndromic and non-syndromic v0.1654 DHPS Zornitza Stark gene: DHPS was added
gene: DHPS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: DHPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHPS were set to 30661771
Phenotypes for gene: DHPS were set to Neurodevelopmental disorder with seizures and speech and walking impairment, MIM#618480
Review for gene: DHPS was set to GREEN
gene: DHPS was marked as current diagnostic
Added comment: 5 individuals from 4 unrelated families with biallelic pathogenic variants in DHPS, note one variant is recurrent (c.518A>G or p.Asn173Ser). The phenotype consisted of DD/ID (5/5), tone abnormalities (hypotonia/hypertonia/spasticity - 5/5), seizures (5/5 - in one case though unclear staring spells) with EEG abnormalities (5/5). Additionally most individuals displayed behavioral issues, or some common facial features
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1653 DHDDS Zornitza Stark Marked gene: DHDDS as ready
Intellectual disability syndromic and non-syndromic v0.1652 DHDDS Zornitza Stark gene: DHDDS was added
gene: DHDDS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: DHDDS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHDDS were set to 29100083
Phenotypes for gene: DHDDS were set to Developmental delay and seizures with or without movement abnormalities, MIM#617836
Review for gene: DHDDS was set to GREEN
gene: DHDDS was marked as current diagnostic
Added comment: Five unrelated individuals reported with mono-allelic variants and a neurodevelopmental phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1651 DEGS1 Zornitza Stark Marked gene: DEGS1 as ready
Intellectual disability syndromic and non-syndromic v0.1650 DEGS1 Zornitza Stark gene: DEGS1 was added
gene: DEGS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: DEGS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DEGS1 were set to 31186544; 30620337; 30620338
Phenotypes for gene: DEGS1 were set to Leukodystrophy hypomyelinating 18, MIM#618404
Review for gene: DEGS1 was set to GREEN
Added comment: Multiple affected families, DD/ID is part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1649 RBFOX1 Zornitza Stark Marked gene: RBFOX1 as ready
Intellectual disability syndromic and non-syndromic v0.1647 DDOST Zornitza Stark Marked gene: DDOST as ready
Intellectual disability syndromic and non-syndromic v0.1643 NTNG1 Zornitza Stark Marked gene: NTNG1 as ready
Intellectual disability syndromic and non-syndromic v0.1642 MTHFS Zornitza Stark Marked gene: MTHFS as ready
Intellectual disability syndromic and non-syndromic v0.1640 CACNA1B Zornitza Stark Marked gene: CACNA1B as ready
Intellectual disability syndromic and non-syndromic v0.1638 CDH2 Zornitza Stark Marked gene: CDH2 as ready
Intellectual disability syndromic and non-syndromic v0.1637 CDH2 Zornitza Stark gene: CDH2 was added
gene: CDH2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDH2 were set to 31585109
Phenotypes for gene: CDH2 were set to Intellectual disability; corpus callosum abnormalities; congenital abnormalities
Review for gene: CDH2 was set to GREEN
Added comment: Nine unrelated individuals reported with de novo variants in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1635 NTNG2 Zornitza Stark Marked gene: NTNG2 as ready
Intellectual disability syndromic and non-syndromic v0.1633 TUBGCP2 Zornitza Stark Marked gene: TUBGCP2 as ready
Intellectual disability syndromic and non-syndromic v0.1631 TP73 Zornitza Stark Marked gene: TP73 as ready
Intellectual disability syndromic and non-syndromic v0.1629 SMG8 Zornitza Stark Marked gene: SMG8 as ready
Intellectual disability syndromic and non-syndromic v0.1627 IQSEC3 Zornitza Stark Marked gene: IQSEC3 as ready
Intellectual disability syndromic and non-syndromic v0.1625 ICE1 Zornitza Stark Marked gene: ICE1 as ready
Intellectual disability syndromic and non-syndromic v0.1624 ICE1 Zornitza Stark gene: ICE1 was added
gene: ICE1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ICE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ICE1 were set to 31130284
Phenotypes for gene: ICE1 were set to Intellectual disability, cerebral atrophy
Review for gene: ICE1 was set to AMBER
Added comment: Two unrelated families reported, no functional data; part of large consanguineous cohort, mixed phenotypes.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1622 EIF2A Alison Yeung Marked gene: EIF2A as ready
Intellectual disability syndromic and non-syndromic v0.1620 KCNN3 Alison Yeung Marked gene: KCNN3 as ready
Intellectual disability syndromic and non-syndromic v0.1619 KCNN3 Alison Yeung gene: KCNN3 was added
gene: KCNN3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNN3 were set to PMID: 31155282
Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3; OMIM# 618658
Review for gene: KCNN3 was set to GREEN
gene: KCNN3 was marked as current diagnostic
Added comment: Reported in three unrelated individuals
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1618 CTNND2 Zornitza Stark Marked gene: CTNND2 as ready
Intellectual disability syndromic and non-syndromic v0.1615 IQSEC1 Zornitza Stark Marked gene: IQSEC1 as ready
Intellectual disability syndromic and non-syndromic v0.1613 POLA1 Alison Yeung Marked gene: POLA1 as ready
Intellectual disability syndromic and non-syndromic v0.1612 POLA1 Alison Yeung gene: POLA1 was added
gene: POLA1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: POLA1 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: POLA1 were set to PMID: 31006512
Phenotypes for gene: POLA1 were set to Van Esch-O'Driscoll syndrome OMIM# 301030
Review for gene: POLA1 was set to GREEN
gene: POLA1 was marked as current diagnostic
Added comment: Five unrelated families reported
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1611 GPC4 Alison Yeung Marked gene: GPC4 as ready
Intellectual disability syndromic and non-syndromic v0.1609 GPC4 Alison Yeung gene: GPC4 was added
gene: GPC4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GPC4 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: GPC4 were set to PMID: 30982611
Phenotypes for gene: GPC4 were set to Keipert syndrome OMIM# 301026
Review for gene: GPC4 was set to GREEN
gene: GPC4 was marked as current diagnostic
Added comment: >3 unrelated individuals reported, functional studies in mice
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1608 CARS Alison Yeung Marked gene: CARS as ready
Intellectual disability syndromic and non-syndromic v0.1608 CARS Alison Yeung Gene: cars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1608 CARS Alison Yeung Classified gene: CARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.1608 CARS Alison Yeung Gene: cars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1607 CARS Alison Yeung gene: CARS was added
gene: CARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARS were set to PMID: 30824121
Phenotypes for gene: CARS were set to Intellectual disability; microcephaly; brittle hair and nails
Review for gene: CARS was set to GREEN
gene: CARS was marked as current diagnostic
Added comment: Three reported unrelated families
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1606 MAPK8IP3 Zornitza Stark Marked gene: MAPK8IP3 as ready
Intellectual disability syndromic and non-syndromic v0.1605 MAPK8IP3 Alison Yeung gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAPK8IP3 were set to 30612693
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities OMIM# 605431
Review for gene: MAPK8IP3 was set to GREEN
gene: MAPK8IP3 was marked as current diagnostic
Added comment: >3 reported individuals and functional evidence in Caenorhabditis elegans
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1604 NCAPG2 Alison Yeung Marked gene: NCAPG2 as ready
Intellectual disability syndromic and non-syndromic v0.1601 RIC1 Zornitza Stark Marked gene: RIC1 as ready
Intellectual disability syndromic and non-syndromic v0.1600 RIC1 Zornitza Stark gene: RIC1 was added
gene: RIC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RIC1 were set to 31932796
Phenotypes for gene: RIC1 were set to Cleft lip; cataract; tooth abnormality; intellectual disability; facial dysmorphism; ADHD
Review for gene: RIC1 was set to AMBER
Added comment: Zebrafish model and consanguineous families but homozygous-by-descent.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1599 TET3 Zornitza Stark Marked gene: TET3 as ready
Intellectual disability syndromic and non-syndromic v0.1598 TET3 Zornitza Stark gene: TET3 was added
gene: TET3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TET3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TET3 were set to 31928709
Phenotypes for gene: TET3 were set to Intellectual disability; dysmorphic features; abnormal growth; movement disorders
Review for gene: TET3 was set to GREEN
Added comment: Eleven individuals from 8 families described. Mono-allelic frameshift and nonsense variants occur throughout the coding region. Mono-allelic and bi-allelic missense variants localize to conserved residues; all but one such variant occur within the catalytic domain, and most display hypomorphic function in an assay of catalytic activity.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1592 HK1 Natasha Brown Marked gene: HK1 as ready
Intellectual disability syndromic and non-syndromic v0.1592 HK1 Natasha Brown gene: HK1 was added
gene: HK1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: HK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HK1 were set to PMID: 30778173
Mode of pathogenicity for gene: HK1 was set to Other
Review for gene: HK1 was set to GREEN
Added comment: 7 patients from 6 unrelated families with denovo missense variants in the N-terminal half of HK1
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1591 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Intellectual disability syndromic and non-syndromic v0.1588 FARSB Zornitza Stark Marked gene: FARSB as ready
Intellectual disability syndromic and non-syndromic v0.1588 FARSB Zornitza Stark Gene: farsb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1588 FARSB Zornitza Stark Classified gene: FARSB as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.1588 FARSB Zornitza Stark Gene: farsb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1587 FARSB Zornitza Stark gene: FARSB was added
gene: FARSB was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: FARSB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARSB were set to 29573043; 19161147; 29979980; 30014610
Phenotypes for gene: FARSB were set to Rajab syndrome, MIM#613658; interstitial lung disease; brain calcifications; microcephaly; intellectual disability
Review for gene: FARSB was set to GREEN
Added comment: 7 unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1586 FAM160B1 Zornitza Stark Marked gene: FAM160B1 as ready
Intellectual disability syndromic and non-syndromic v0.1586 CLCNKB Zornitza Stark Marked gene: CLCNKB as ready
Intellectual disability syndromic and non-syndromic v0.1586 CLCNKB Zornitza Stark Phenotypes for gene: CLCNKB were changed from Bartter syndrome, type 3, MIM#607364; Bartter syndrome, type 4b, digenic, MIM#613090 to Bartter syndrome, type 3, MIM#607364; Bartter syndrome, type 4b, digenic, MIM#613090
Intellectual disability syndromic and non-syndromic v0.1585 CLCNKB Zornitza Stark Phenotypes for gene: CLCNKB were changed from to Bartter syndrome, type 3, MIM#607364; Bartter syndrome, type 4b, digenic, MIM#613090
Intellectual disability syndromic and non-syndromic v0.1584 AP1B1 Zornitza Stark Marked gene: AP1B1 as ready
Intellectual disability syndromic and non-syndromic v0.1584 CLCNKA Zornitza Stark Marked gene: CLCNKA as ready
Intellectual disability syndromic and non-syndromic v0.1582 CLCNKA Zornitza Stark Phenotypes for gene: CLCNKA were changed from to Bartter syndrome, type 4b, digenic, MIM#613090
Intellectual disability syndromic and non-syndromic v0.1582 COASY Zornitza Stark Marked gene: COASY as ready
Intellectual disability syndromic and non-syndromic v0.1580 COASY Zornitza Stark Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6 615643; Pontocerebellar hypoplasia, type 12 618266 to Neurodegeneration with brain iron accumulation 6 615643; Pontocerebellar hypoplasia, type 12 618266
Intellectual disability syndromic and non-syndromic v0.1579 COG6 Zornitza Stark Marked gene: COG6 as ready
Intellectual disability syndromic and non-syndromic v0.1579 COASY Zornitza Stark Phenotypes for gene: COASY were changed from to Neurodegeneration with brain iron accumulation 6 615643; Pontocerebellar hypoplasia, type 12 618266
Intellectual disability syndromic and non-syndromic v0.1576 COQ9 Zornitza Stark Marked gene: COQ9 as ready
Intellectual disability syndromic and non-syndromic v0.1576 COQ9 Zornitza Stark Phenotypes for gene: COQ9 were changed from to Coenzyme Q10 deficiency, primary, 5, MIM#614654
Intellectual disability syndromic and non-syndromic v0.1574 ETFA Zornitza Stark Marked gene: ETFA as ready
Intellectual disability syndromic and non-syndromic v0.1574 ETFDH Zornitza Stark Marked gene: ETFDH as ready
Intellectual disability syndromic and non-syndromic v0.1574 FARS2 Zornitza Stark Marked gene: FARS2 as ready
Intellectual disability syndromic and non-syndromic v0.1574 FARS2 Zornitza Stark Gene: fars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1574 MAP1B Zornitza Stark Marked gene: MAP1B as ready
Intellectual disability syndromic and non-syndromic v0.1574 KLF7 Zornitza Stark Marked gene: KLF7 as ready
Intellectual disability syndromic and non-syndromic v0.1571 MED17 Zornitza Stark Marked gene: MED17 as ready
Intellectual disability syndromic and non-syndromic v0.1568 METTL5 Zornitza Stark Marked gene: METTL5 as ready
Intellectual disability syndromic and non-syndromic v0.1568 MPDZ Zornitza Stark Marked gene: MPDZ as ready
Intellectual disability syndromic and non-syndromic v0.1568 NDUFA2 Zornitza Stark Marked gene: NDUFA2 as ready
Intellectual disability syndromic and non-syndromic v0.1568 MPV17 Zornitza Stark Marked gene: MPV17 as ready
Intellectual disability syndromic and non-syndromic v0.1568 NDUFA2 Zornitza Stark Phenotypes for gene: NDUFA2 were changed from to Mitochondrial complex I deficiency, nuclear type 13, MIM#618235
Intellectual disability syndromic and non-syndromic v0.1567 MTO1 Zornitza Stark Marked gene: MTO1 as ready
Intellectual disability syndromic and non-syndromic v0.1566 NDUFAF1 Zornitza Stark Marked gene: NDUFAF1 as ready
Intellectual disability syndromic and non-syndromic v0.1566 NDUFAF1 Zornitza Stark Phenotypes for gene: NDUFAF1 were changed from to Mitochondrial complex I deficiency, nuclear type 11, MIM#618234
Intellectual disability syndromic and non-syndromic v0.1563 PIGG Zornitza Stark Marked gene: PIGG as ready
Intellectual disability syndromic and non-syndromic v0.1563 PIGG Zornitza Stark Phenotypes for gene: PIGG were changed from Mental retardation, autosomal recessive 53, MIM#616917 to Mental retardation, autosomal recessive 53, MIM#616917
Intellectual disability syndromic and non-syndromic v0.1562 PIGG Zornitza Stark Phenotypes for gene: PIGG were changed from to Mental retardation, autosomal recessive 53, MIM#616917
Intellectual disability syndromic and non-syndromic v0.1558 PPP2CA Zornitza Stark Marked gene: PPP2CA as ready
Intellectual disability syndromic and non-syndromic v0.1558 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
Intellectual disability syndromic and non-syndromic v0.1558 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1558 RTN4IP1 Zornitza Stark Marked gene: RTN4IP1 as ready
Intellectual disability syndromic and non-syndromic v0.1558 SCAPER Zornitza Stark Marked gene: SCAPER as ready
Intellectual disability syndromic and non-syndromic v0.1558 SCN9A Zornitza Stark Marked gene: SCN9A as ready
Intellectual disability syndromic and non-syndromic v0.1555 SEMA3E Zornitza Stark Marked gene: SEMA3E as ready
Intellectual disability syndromic and non-syndromic v0.1555 SEMA3E Zornitza Stark Phenotypes for gene: SEMA3E were changed from CHARGE syndrome, MIM#214800 to CHARGE syndrome, MIM#214800
Intellectual disability syndromic and non-syndromic v0.1554 SEMA3E Zornitza Stark Phenotypes for gene: SEMA3E were changed from to CHARGE syndrome, MIM#214800
Intellectual disability syndromic and non-syndromic v0.1552 SMPD4 Zornitza Stark Marked gene: SMPD4 as ready
Intellectual disability syndromic and non-syndromic v0.1552 SMPD4 Zornitza Stark Phenotypes for gene: SMPD4 were changed from Severe neurodevelopmental delay, microcephaly, arthrogryposis to Severe neurodevelopmental delay, microcephaly, arthrogryposis
Intellectual disability syndromic and non-syndromic v0.1551 SMPD4 Zornitza Stark Phenotypes for gene: SMPD4 were changed from to Severe neurodevelopmental delay, microcephaly, arthrogryposis
Intellectual disability syndromic and non-syndromic v0.1548 SNAP25 Zornitza Stark Marked gene: SNAP25 as ready
Intellectual disability syndromic and non-syndromic v0.1548 SOX4 Zornitza Stark Marked gene: SOX4 as ready
Intellectual disability syndromic and non-syndromic v0.1548 SPART Zornitza Stark Marked gene: SPART as ready
Intellectual disability syndromic and non-syndromic v0.1548 SPART Zornitza Stark Gene: spart has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1548 SPG7 Zornitza Stark Marked gene: SPG7 as ready
Intellectual disability syndromic and non-syndromic v0.1548 ST3GAL5 Zornitza Stark Marked gene: ST3GAL5 as ready
Intellectual disability syndromic and non-syndromic v0.1548 SUCLA2 Zornitza Stark Marked gene: SUCLA2 as ready
Intellectual disability syndromic and non-syndromic v0.1548 SUMF1 Zornitza Stark Marked gene: SUMF1 as ready
Intellectual disability syndromic and non-syndromic v0.1548 SUZ12 Zornitza Stark Marked gene: SUZ12 as ready
Intellectual disability syndromic and non-syndromic v0.1548 SVBP Zornitza Stark Marked gene: SVBP as ready
Intellectual disability syndromic and non-syndromic v0.1548 SYT1 Zornitza Stark Marked gene: SYT1 as ready
Intellectual disability syndromic and non-syndromic v0.1548 TBC1D20 Zornitza Stark Marked gene: TBC1D20 as ready
Intellectual disability syndromic and non-syndromic v0.1548 TBCD Zornitza Stark Phenotypes for gene: TBCD were changed from Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, MIM#617193 to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, MIM#617193
Intellectual disability syndromic and non-syndromic v0.1548 TBCD Zornitza Stark Marked gene: TBCD as ready
Intellectual disability syndromic and non-syndromic v0.1548 TBCD Zornitza Stark Phenotypes for gene: TBCD were changed from to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, MIM#617193
Intellectual disability syndromic and non-syndromic v0.1545 TDP2 Zornitza Stark Marked gene: TDP2 as ready
Intellectual disability syndromic and non-syndromic v0.1545 TERT Zornitza Stark Marked gene: TERT as ready
Intellectual disability syndromic and non-syndromic v0.1545 TKT Zornitza Stark Marked gene: TKT as ready
Intellectual disability syndromic and non-syndromic v0.1545 TPP1 Zornitza Stark Marked gene: TPP1 as ready
Intellectual disability syndromic and non-syndromic v0.1545 TRAF7 Zornitza Stark Marked gene: TRAF7 as ready
Intellectual disability syndromic and non-syndromic v0.1545 TRAPPC11 Zornitza Stark Marked gene: TRAPPC11 as ready
Intellectual disability syndromic and non-syndromic v0.1545 TRMT1 Zornitza Stark Marked gene: TRMT1 as ready
Intellectual disability syndromic and non-syndromic v0.1545 TRNT1 Zornitza Stark Marked gene: TRNT1 as ready
Intellectual disability syndromic and non-syndromic v0.1545 TRRAP Zornitza Stark Marked gene: TRRAP as ready
Intellectual disability syndromic and non-syndromic v0.1545 UFM1 Zornitza Stark Marked gene: UFM1 as ready
Intellectual disability syndromic and non-syndromic v0.1545 VARS2 Zornitza Stark Marked gene: VARS2 as ready
Intellectual disability syndromic and non-syndromic v0.1545 VARS2 Zornitza Stark Gene: vars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1545 VIPAS39 Zornitza Stark Marked gene: VIPAS39 as ready
Intellectual disability syndromic and non-syndromic v0.1545 VPS33B Zornitza Stark Marked gene: VPS33B as ready
Intellectual disability syndromic and non-syndromic v0.1545 VPS37A Zornitza Stark Marked gene: VPS37A as ready
Intellectual disability syndromic and non-syndromic v0.1545 WDR37 Zornitza Stark Marked gene: WDR37 as ready
Intellectual disability syndromic and non-syndromic v0.1545 WNT1 Zornitza Stark Marked gene: WNT1 as ready
Intellectual disability syndromic and non-syndromic v0.1545 WNT5A Zornitza Stark Marked gene: WNT5A as ready
Intellectual disability syndromic and non-syndromic v0.1545 XPA Zornitza Stark Marked gene: XPA as ready
Intellectual disability syndromic and non-syndromic v0.1545 XYLT1 Zornitza Stark Marked gene: XYLT1 as ready
Intellectual disability syndromic and non-syndromic v0.1545 ZNF335 Zornitza Stark Marked gene: ZNF335 as ready
Intellectual disability syndromic and non-syndromic v0.1545 ZSWIM6 Zornitza Stark Marked gene: ZSWIM6 as ready
Intellectual disability syndromic and non-syndromic v0.1541 MAGT1 Zornitza Stark Marked gene: MAGT1 as ready
Intellectual disability syndromic and non-syndromic v0.1541 MRPL3 Zornitza Stark Marked gene: MRPL3 as ready
Intellectual disability syndromic and non-syndromic v0.1541 NDUFB9 Zornitza Stark Marked gene: NDUFB9 as ready
Intellectual disability syndromic and non-syndromic v0.1540 SLC35A3 Zornitza Stark Marked gene: SLC35A3 as ready
Intellectual disability syndromic and non-syndromic v0.1540 SLC9A7 Zornitza Stark Marked gene: SLC9A7 as ready
Intellectual disability syndromic and non-syndromic v0.1540 SNRPN Zornitza Stark Marked gene: SNRPN as ready
Intellectual disability syndromic and non-syndromic v0.1540 TACO1 Zornitza Stark Marked gene: TACO1 as ready
Intellectual disability syndromic and non-syndromic v0.1540 TCTN3 Zornitza Stark Marked gene: TCTN3 as ready
Intellectual disability syndromic and non-syndromic v0.1539 TMEM231 Zornitza Stark Marked gene: TMEM231 as ready
Intellectual disability syndromic and non-syndromic v0.1539 TUFM Zornitza Stark Marked gene: TUFM as ready
Intellectual disability syndromic and non-syndromic v0.1539 UQCC2 Zornitza Stark Marked gene: UQCC2 as ready
Intellectual disability syndromic and non-syndromic v0.1539 ZC3H14 Zornitza Stark Marked gene: ZC3H14 as ready
Intellectual disability syndromic and non-syndromic v0.1539 ATP6AP1 Zornitza Stark Marked gene: ATP6AP1 as ready
Intellectual disability syndromic and non-syndromic v0.1538 EIF2B5 Zornitza Stark Marked gene: EIF2B5 as ready
Intellectual disability syndromic and non-syndromic v0.1538 IGF2 Zornitza Stark Marked gene: IGF2 as ready
Intellectual disability syndromic and non-syndromic v0.1538 KLLN Zornitza Stark Marked gene: KLLN as ready
Intellectual disability syndromic and non-syndromic v0.1538 LSM1 Zornitza Stark Marked gene: LSM1 as ready
Intellectual disability syndromic and non-syndromic v0.1538 MACROD2 Zornitza Stark Marked gene: MACROD2 as ready
Intellectual disability syndromic and non-syndromic v0.1538 MCM4 Zornitza Stark Marked gene: MCM4 as ready
Intellectual disability syndromic and non-syndromic v0.1538 MET Zornitza Stark Marked gene: MET as ready
Intellectual disability syndromic and non-syndromic v0.1538 MFN2 Zornitza Stark Marked gene: MFN2 as ready
Intellectual disability syndromic and non-syndromic v0.1538 MGME1 Zornitza Stark Marked gene: MGME1 as ready
Intellectual disability syndromic and non-syndromic v0.1538 MGP Zornitza Stark Marked gene: MGP as ready
Intellectual disability syndromic and non-syndromic v0.1538 MID2 Zornitza Stark Marked gene: MID2 as ready
Intellectual disability syndromic and non-syndromic v0.1538 MLH1 Zornitza Stark Marked gene: MLH1 as ready
Intellectual disability syndromic and non-syndromic v0.1538 MNX1 Zornitza Stark Marked gene: MNX1 as ready
Intellectual disability syndromic and non-syndromic v0.1538 MPZ Zornitza Stark Marked gene: MPZ as ready
Intellectual disability syndromic and non-syndromic v0.1538 MRAP Zornitza Stark Marked gene: MRAP as ready
Intellectual disability syndromic and non-syndromic v0.1538 AGMO Zornitza Stark Marked gene: AGMO as ready
Intellectual disability syndromic and non-syndromic v0.1538 AGMO Zornitza Stark Added comment: Comment when marking as ready: Three unrelated families and functional data.
Intellectual disability syndromic and non-syndromic v0.1537 AGMO Sue White Marked gene: AGMO as ready
Intellectual disability syndromic and non-syndromic v0.1536 AGMO Sue White gene: AGMO was added
gene: AGMO was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: AGMO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGMO were set to 31555905
Phenotypes for gene: AGMO were set to microcephaly; intellectual disability; epilepsy
Penetrance for gene: AGMO were set to Complete
Review for gene: AGMO was set to GREEN
Added comment: biallelic missense and LOF variants reported
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1535 STAG2 Zornitza Stark Marked gene: STAG2 as ready
Intellectual disability syndromic and non-syndromic v0.1535 STAG2 Zornitza Stark Phenotypes for gene: STAG2 were changed from to Mullegama-Klein-Martinez syndrome, MIM#301022
Intellectual disability syndromic and non-syndromic v0.1533 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Intellectual disability syndromic and non-syndromic v0.1533 FOXP1 Zornitza Stark Phenotypes for gene: FOXP1 were changed from to Mental retardation with language impairment and with or without autistic features, MIM# 613670
Intellectual disability syndromic and non-syndromic v0.1530 FOXP1 Michelle Torres reviewed gene: FOXP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26633542, PMID: 28741757; Phenotypes: Mental retardation with language impairment and with or without autistic features 613670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.1530 COASY Michelle Torres reviewed gene: COASY: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24360804, PMID: 30089828; Phenotypes: Neurodegeneration with brain iron accumulation 6 615643, Pontocerebellar hypoplasia, type 12 618266; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1530 NUP214 Zornitza Stark Marked gene: NUP214 as ready
Intellectual disability syndromic and non-syndromic v0.1530 NUP214 Zornitza Stark Added comment: Comment when marking as ready: Three unrelated families reported.
Intellectual disability syndromic and non-syndromic v0.1529 EXTL3 Zornitza Stark Marked gene: EXTL3 as ready
Intellectual disability syndromic and non-syndromic v0.1525 NUP214 Sue White Marked gene: NUP214 as ready
Intellectual disability syndromic and non-syndromic v0.1524 NUP214 Sue White gene: NUP214 was added
gene: NUP214 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: NUP214 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP214 were set to 31178128
Phenotypes for gene: NUP214 were set to epileptic encephalopathy; developmental regression; microcephaly
Penetrance for gene: NUP214 were set to Complete
Review for gene: NUP214 was set to GREEN
gene: NUP214 was marked as current diagnostic
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1523 AP2M1 Zornitza Stark Marked gene: AP2M1 as ready
Intellectual disability syndromic and non-syndromic v0.1522 AP2M1 Zornitza Stark gene: AP2M1 was added
gene: AP2M1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: AP2M1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AP2M1 were set to 31104773
Phenotypes for gene: AP2M1 were set to Intellectual developmental disorder 60 with seizures, MIM# 618587
Review for gene: AP2M1 was set to GREEN
Added comment: Four unrelated individuals reported, recurrent variant, NM_004068.3:c.508C>T or p.Arg170Trp.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1520 ASXL3 Zornitza Stark Marked gene: ASXL3 as ready
Intellectual disability syndromic and non-syndromic v0.1517 WDFY3 Zornitza Stark Marked gene: WDFY3 as ready
Intellectual disability syndromic and non-syndromic v0.1517 WDFY3 Zornitza Stark Phenotypes for gene: WDFY3 were changed from to Microcephaly 18, primary, autosomal dominant, MIM#617520
Intellectual disability syndromic and non-syndromic v0.1514 DNMT3A Zornitza Stark Phenotypes for gene: DNMT3A were changed from Gatton-Brown-Rahman syndrome, MIM#615879; primordial dwarfism with intellectual disability and microcephaly to Tatton-Brown-Rahman syndrome, MIM#615879; primordial dwarfism with intellectual disability and microcephaly
Intellectual disability syndromic and non-syndromic v0.1513 DNMT3A Zornitza Stark Marked gene: DNMT3A as ready
Intellectual disability syndromic and non-syndromic v0.1513 DNMT3A Zornitza Stark Phenotypes for gene: DNMT3A were changed from to Gatton-Brown-Rahman syndrome, MIM#615879; primordial dwarfism with intellectual disability and microcephaly
Intellectual disability syndromic and non-syndromic v0.1510 DNMT3A Zornitza Stark reviewed gene: DNMT3A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30478443, 24614070; Phenotypes: TATTON-BROWN-RAHMAN SYNDROME, OMIM# 615879, primordial dwarfism with intellectual disability and microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1510 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Intellectual disability syndromic and non-syndromic v0.1507 FZD3 Zornitza Stark Marked gene: FZD3 as ready
Intellectual disability syndromic and non-syndromic v0.1506 H3F3A Zornitza Stark Marked gene: H3F3A as ready
Intellectual disability syndromic and non-syndromic v0.1504 H3F3B Zornitza Stark commented on gene: H3F3B: Elizabeth J Bhoj, H3F3A/B Consortium, Hakon H. Hakonarson.: Mutations In H3f3a And H3f3b Encoding Histone 3.3: Report Of 26 Patients With Neurodevelopmental And Congenital Manifestations. American Society of Human Genetics, Orlando, FL October 2017 Notes: Platform Presentation.
Intellectual disability syndromic and non-syndromic v0.1504 KAT5 Zornitza Stark Marked gene: KAT5 as ready
Intellectual disability syndromic and non-syndromic v0.1504 KAT5 Zornitza Stark Added comment: Comment when marking as ready: Cannot find evidence for Mendelian gene-disease association.
Intellectual disability syndromic and non-syndromic v0.1503 MRPS16 Zornitza Stark Marked gene: MRPS16 as ready
Intellectual disability syndromic and non-syndromic v0.1503 MSH6 Zornitza Stark Marked gene: MSH6 as ready
Intellectual disability syndromic and non-syndromic v0.1503 MTM1 Zornitza Stark Marked gene: MTM1 as ready
Intellectual disability syndromic and non-syndromic v0.1503 MTMR2 Zornitza Stark Marked gene: MTMR2 as ready
Intellectual disability syndromic and non-syndromic v0.1503 MTPAP Zornitza Stark Marked gene: MTPAP as ready
Intellectual disability syndromic and non-syndromic v0.1503 MYH3 Zornitza Stark Marked gene: MYH3 as ready
Intellectual disability syndromic and non-syndromic v0.1503 MYMK Zornitza Stark Marked gene: MYMK as ready
Intellectual disability syndromic and non-syndromic v0.1503 MYO7A Zornitza Stark Marked gene: MYO7A as ready
Intellectual disability syndromic and non-syndromic v0.1503 ORC4 Zornitza Stark Marked gene: ORC4 as ready
Intellectual disability syndromic and non-syndromic v0.1503 ORC6 Zornitza Stark Marked gene: ORC6 as ready
Intellectual disability syndromic and non-syndromic v0.1503 PCBD1 Zornitza Stark Marked gene: PCBD1 as ready
Intellectual disability syndromic and non-syndromic v0.1503 SLC29A3 Zornitza Stark Marked gene: SLC29A3 as ready
Intellectual disability syndromic and non-syndromic v0.1503 SLC2A10 Zornitza Stark Marked gene: SLC2A10 as ready
Intellectual disability syndromic and non-syndromic v0.1503 SLC39A4 Zornitza Stark Marked gene: SLC39A4 as ready
Intellectual disability syndromic and non-syndromic v0.1503 SLC5A2 Zornitza Stark Marked gene: SLC5A2 as ready
Intellectual disability syndromic and non-syndromic v0.1503 SMCHD1 Zornitza Stark Marked gene: SMCHD1 as ready
Intellectual disability syndromic and non-syndromic v0.1503 SMG6 Zornitza Stark Marked gene: SMG6 as ready
Intellectual disability syndromic and non-syndromic v0.1503 SNRPA Zornitza Stark Marked gene: SNRPA as ready
Intellectual disability syndromic and non-syndromic v0.1503 EDC3 Zornitza Stark Marked gene: EDC3 as ready
Intellectual disability syndromic and non-syndromic v0.1503 EDC3 Zornitza Stark gene: EDC3 was added
gene: EDC3 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: EDC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EDC3 were set to 29685133; 25701870
Phenotypes for gene: EDC3 were set to Mental retardation, autosomal recessive 50, MIM# 616460
Review for gene: EDC3 was set to RED
Added comment: Single family reported; some functional data.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1502 PUS3 Zornitza Stark Marked gene: PUS3 as ready
Intellectual disability syndromic and non-syndromic v0.1501 PUS3 Zornitza Stark gene: PUS3 was added
gene: PUS3 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: PUS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS3 were set to 30308082; 28454995; 27055666; 30697592; 31444731
Phenotypes for gene: PUS3 were set to Mental retardation, autosomal recessive 55, MIM# 617051
Review for gene: PUS3 was set to GREEN
Added comment: Seven individuals from five families reported; two of the families had the same homozygous truncating variant. Variable features reported in addition to ID, including leukoencephalopathy, EE, and nephropathy.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1500 EIF3F Zornitza Stark Marked gene: EIF3F as ready
Intellectual disability syndromic and non-syndromic v0.1499 EIF3F Zornitza Stark gene: EIF3F was added
gene: EIF3F was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to 30409806
Phenotypes for gene: EIF3F were set to Mental retardation, autosomal recessive 67, MIM# 618295
Review for gene: EIF3F was set to GREEN
Added comment: Nine individuals from 7 families reported, all homozygous for the same missense variant, p.(Phe232Val). This variant is present at 0.12% frequency in non-Finnish Europeans in gnomad (no homozygotes).
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1498 RUSC2 Zornitza Stark Marked gene: RUSC2 as ready
Intellectual disability syndromic and non-syndromic v0.1497 RUSC2 Zornitza Stark gene: RUSC2 was added
gene: RUSC2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: RUSC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RUSC2 were set to 27612186
Phenotypes for gene: RUSC2 were set to Mental retardation, autosomal recessive 61, MIM# 617773
Review for gene: RUSC2 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1496 RSRC1 Zornitza Stark Marked gene: RSRC1 as ready
Intellectual disability syndromic and non-syndromic v0.1492 CXorf56 Zornitza Stark Marked gene: CXorf56 as ready
Intellectual disability syndromic and non-syndromic v0.1492 CXorf56 Zornitza Stark gene: CXorf56 was added
gene: CXorf56 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: CXorf56 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CXorf56 were set to 29374277
Phenotypes for gene: CXorf56 were set to Mental retardation, X-linked 107, MIM# 301013
Review for gene: CXorf56 was set to RED
Added comment: Single multigenerational family reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1491 USP27X Zornitza Stark Marked gene: USP27X as ready
Intellectual disability syndromic and non-syndromic v0.1490 USP27X Zornitza Stark gene: USP27X was added
gene: USP27X was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: USP27X was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: USP27X were set to 25644381
Phenotypes for gene: USP27X were set to Mental retardation, X-linked 105, MIM#300984
Review for gene: USP27X was set to AMBER
Added comment: Four individuals from two unrelated families reported.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1489 KLHL15 Zornitza Stark Marked gene: KLHL15 as ready
Intellectual disability syndromic and non-syndromic v0.1488 KLHL15 Zornitza Stark gene: KLHL15 was added
gene: KLHL15 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: KLHL15 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KLHL15 were set to 25644381; 24817631
Phenotypes for gene: KLHL15 were set to Mental retardation, X-linked 103, MIM#300982
Review for gene: KLHL15 was set to AMBER
Added comment: Two families described: variants maternally inherited in both, one deletion, the other truncating.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1487 ODC1 Zornitza Stark Marked gene: ODC1 as ready
Intellectual disability syndromic and non-syndromic v0.1486 ODC1 Zornitza Stark gene: ODC1 was added
gene: ODC1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: ODC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ODC1 were set to 30475435
Phenotypes for gene: ODC1 were set to Intellectual disability; macrocephaly; dysmorphism
Mode of pathogenicity for gene: ODC1 was set to Other
Review for gene: ODC1 was set to GREEN
Added comment: Four individuals with de novo GoF variants in this gene reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1485 RALA Zornitza Stark Marked gene: RALA as ready
Intellectual disability syndromic and non-syndromic v0.1484 RALA Zornitza Stark gene: RALA was added
gene: RALA was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: RALA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RALA were set to 30500825
Phenotypes for gene: RALA were set to Intellectual disability; short stature; dysmorphism
Review for gene: RALA was set to GREEN
Added comment: Ten individuals with de novo variants in this gene, six of these at two codons only: Val25 and Lys128.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1483 LSS Zornitza Stark Phenotypes for gene: LSS were changed from Cataract 44, OMIM #616509; Hypotrichosis 14, OMIM #618275 to Cataract 44, OMIM #616509; Hypotrichosis 14, OMIM #618275; intellectual disability and alopecia
Intellectual disability syndromic and non-syndromic v0.1482 TRPM3 Zornitza Stark Marked gene: TRPM3 as ready
Intellectual disability syndromic and non-syndromic v0.1481 TRPM3 Zornitza Stark gene: TRPM3 was added
gene: TRPM3 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM3 were set to 31278393
Phenotypes for gene: TRPM3 were set to Intellectual disability; epilepsy
Review for gene: TRPM3 was set to GREEN
Added comment: 8 unrelated individuals with de novo variants in this gene. Recurrent variant p.(Val837Met) identified in 7/8.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1480 TANC2 Zornitza Stark Marked gene: TANC2 as ready
Intellectual disability syndromic and non-syndromic v0.1479 NUS1 Zornitza Stark Marked gene: NUS1 as ready
Intellectual disability syndromic and non-syndromic v0.1478 NUS1 Zornitza Stark gene: NUS1 was added
gene: NUS1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUS1 were set to 31656175; 29100083
Phenotypes for gene: NUS1 were set to Epilepsy; intellectual disability
Review for gene: NUS1 was set to GREEN
Added comment: Five individuals reported with de novo variants in this gene and epilepsy/ID phenotype (4 truncating variants and a small deletion).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1477 UGP2 Zornitza Stark Marked gene: UGP2 as ready
Intellectual disability syndromic and non-syndromic v0.1476 UGP2 Zornitza Stark gene: UGP2 was added
gene: UGP2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: UGP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UGP2 were set to 31820119
Phenotypes for gene: UGP2 were set to Epileptic encephalopathy; intellectual disability; microcephaly
Review for gene: UGP2 was set to GREEN
Added comment: 22 individuals from 15 families reported with the same homozygous missense variant in this gene, chr2:64083454A > G, which causes a disruption of the start codon in the shorter isoform, which is expressed in brain.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1474 TRIM32 Zornitza Stark Marked gene: TRIM32 as ready
Intellectual disability syndromic and non-syndromic v0.1474 TRIM32 Zornitza Stark Phenotypes for gene: TRIM32 were changed from to Bardet-Biedl syndrome 11, MIM# 615988
Intellectual disability syndromic and non-syndromic v0.1470 TRIM32 Zornitza Stark reviewed gene: TRIM32: Rating: RED; Mode of pathogenicity: None; Publications: 16606853; Phenotypes: Bardet-Biedl syndrome 11, MIM# 615988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1470 XPNPEP3 Zornitza Stark Marked gene: XPNPEP3 as ready
Intellectual disability syndromic and non-syndromic v0.1466 NTRK2 Zornitza Stark Marked gene: NTRK2 as ready
Intellectual disability syndromic and non-syndromic v0.1464 GLS Zornitza Stark Marked gene: GLS as ready
Intellectual disability syndromic and non-syndromic v0.1463 GLS Zornitza Stark gene: GLS was added
gene: GLS was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLS were set to 30970188
Phenotypes for gene: GLS were set to Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412
Review for gene: GLS was set to AMBER
Added comment: Three unrelated individuals described with compound het variants, however, note one of these is a triplet expansion in the 5' UTR, this may not be tractable depending on sequencing modality.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1462 PPP1R12A Zornitza Stark Marked gene: PPP1R12A as ready
Intellectual disability syndromic and non-syndromic v0.1462 PPP1R12A Zornitza Stark Added comment: Comment when marking as ready: Now published, 12 individuals, upgraded to Green.
Intellectual disability syndromic and non-syndromic v0.1460 PUM1 Zornitza Stark Marked gene: PUM1 as ready
Intellectual disability syndromic and non-syndromic v0.1460 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM#617931 to Spinocerebellar ataxia 47, MIM#617931; intellectual disability; epilepsy
Intellectual disability syndromic and non-syndromic v0.1457 SHANK1 Zornitza Stark Marked gene: SHANK1 as ready
Intellectual disability syndromic and non-syndromic v0.1453 AP1B1 Zornitza Stark gene: AP1B1 was added
gene: AP1B1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1B1 were set to 31630788; 31630791
Phenotypes for gene: AP1B1 were set to Intellectual disability; enteropathy; deafness; ichthyosis; keratoderma
Review for gene: AP1B1 was set to GREEN
Added comment: Four unrelated families with bi-allelic LoF variants in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1452 DMXL2 Zornitza Stark Marked gene: DMXL2 as ready
Intellectual disability syndromic and non-syndromic v0.1451 DMXL2 Zornitza Stark gene: DMXL2 was added
gene: DMXL2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: DMXL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMXL2 were set to 31688942; 30237576
Phenotypes for gene: DMXL2 were set to Epileptic encephalopathy, early infantile, 81, MIM# 618663
Review for gene: DMXL2 was set to GREEN
Added comment: Four unrelated families reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1450 NUP188 Zornitza Stark Marked gene: NUP188 as ready
Intellectual disability syndromic and non-syndromic v0.1449 SLC5A6 Zornitza Stark Marked gene: SLC5A6 as ready
Intellectual disability syndromic and non-syndromic v0.1447 NUP188 Zornitza Stark Phenotypes for gene: NUP188 were changed from to microcephaly; ID; cataract
Intellectual disability syndromic and non-syndromic v0.1444 NUP188 Zornitza Stark reviewed gene: NUP188: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1159/000504818, 28726809; Phenotypes: microcephaly, ID, cataract; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1444 CCDC88C Zornitza Stark Marked gene: CCDC88C as ready
Intellectual disability syndromic and non-syndromic v0.1443 CCDC88C Zornitza Stark Phenotypes for gene: CCDC88C were changed from to Spinocerebellar ataxia 40, MIM#616053
Intellectual disability syndromic and non-syndromic v0.1440 CCDC88C Zornitza Stark reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 25062847, 30398676; Phenotypes: Spinocerebellar ataxia 40, MIM#616053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1440 COQ5 Zornitza Stark Marked gene: COQ5 as ready
Intellectual disability syndromic and non-syndromic v0.1440 COQ5 Zornitza Stark Phenotypes for gene: COQ5 were changed from to Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability
Intellectual disability syndromic and non-syndromic v0.1436 COQ5 Zornitza Stark reviewed gene: COQ5: Rating: RED; Mode of pathogenicity: None; Publications: 29044765; Phenotypes: Cerebellar ataxia, encephalopathy, generalized tonic-clonic seizures, intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1436 MN1 Zornitza Stark Marked gene: MN1 as ready
Intellectual disability syndromic and non-syndromic v0.1435 MN1 Zornitza Stark gene: MN1 was added
gene: MN1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: MN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MN1 were set to 31834374; 31839203
Phenotypes for gene: MN1 were set to Intellectual disability; dysmophic features; rhombencephalosynapsis
Mode of pathogenicity for gene: MN1 was set to Other
Review for gene: MN1 was set to GREEN
Added comment: Over 20 individuals described with de novo truncating variants in this gene; these cluster in the C-terminal and the authors postulate that that syndrome is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1434 EEF1B2 Zornitza Stark Marked gene: EEF1B2 as ready
Intellectual disability syndromic and non-syndromic v0.1433 EEF1B2 Zornitza Stark gene: EEF1B2 was added
gene: EEF1B2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: EEF1B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEF1B2 were set to 31845318; 21937992
Phenotypes for gene: EEF1B2 were set to Intellectual disability
Review for gene: EEF1B2 was set to AMBER
Added comment: 5 individuals from two unrelated families described in the literature so far, no functional data but gene belongs to a family implicated in neurodevelopmental disorders.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1432 CLCN4 Zornitza Stark Marked gene: CLCN4 as ready
Intellectual disability syndromic and non-syndromic v0.1432 CLCN4 Zornitza Stark Phenotypes for gene: CLCN4 were changed from to Raynaud-Claes syndrome, MIM#300114; intellectual disability; epilepsy; autistic features; mood disorders; cerebral white matter changes; progressive appendicular spasticity
Intellectual disability syndromic and non-syndromic v0.1429 CLCN4 Elizabeth Palmer reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 27550844); Phenotypes: intellectual disability, epilepsy, autistic features, mood disorders, cerebral white matter changes, progressive appendicular spasticity; 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 v0.1429 ATP1A1 Zornitza Stark Marked gene: ATP1A1 as ready
Intellectual disability syndromic and non-syndromic v0.1428 ATP1A1 Zornitza Stark gene: ATP1A1 was added
gene: ATP1A1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: ATP1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A1 were set to 30388404
Phenotypes for gene: ATP1A1 were set to Intellectual disability; seizures; hypomagnesaemia
Review for gene: ATP1A1 was set to GREEN
Added comment: Three infants with de novo missense variants in this gene; seizures persisted despite correction of magnesium, intellectual disability is part of the phenotype. Note gene is also linked to CMT and possibly HSP.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1427 TASP1 Zornitza Stark Marked gene: TASP1 as ready
Intellectual disability syndromic and non-syndromic v0.1426 TASP1 Zornitza Stark gene: TASP1 was added
gene: TASP1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: TASP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TASP1 were set to 31209944; 31350873
Phenotypes for gene: TASP1 were set to Developmental delay; microcephaly; dysmorphic features; congenital abnormalities
Review for gene: TASP1 was set to GREEN
Added comment: 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
Intellectual disability syndromic and non-syndromic v0.1425 CACNA1G Chris Richmond reviewed gene: CACNA1G: Rating: ; Mode of pathogenicity: Other; Publications: 29878067, 31836334; Phenotypes: Spinocerebellar ataxia 42 [616795], Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits [618087], Infantile-Onset Syndromic Cerebellar Ataxia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.1425 SOST Zornitza Stark Marked gene: SOST as ready
Intellectual disability syndromic and non-syndromic v0.1424 HNRNPR Zornitza Stark Marked gene: HNRNPR as ready
Intellectual disability syndromic and non-syndromic v0.1423 HNRNPR Zornitza Stark gene: HNRNPR was added
gene: HNRNPR was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: HNRNPR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPR were set to 31079900
Phenotypes for gene: HNRNPR were set to Intellectual disability; seizures; dysmorphic features
Review for gene: HNRNPR was set to GREEN
Added comment: Four unrelated families with heterozygous variants in this gene and a neurodevelopmental phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1422 DSCAM Natasha Brown Marked gene: DSCAM as ready
Intellectual disability syndromic and non-syndromic v0.1422 DSCAM Natasha Brown Added comment: Comment when marking as ready: Large cohort studies mean that individual phenotype data currently lacking in particular in relation to ID
Intellectual disability syndromic and non-syndromic v0.1418 PPP1R12A Zornitza Stark Marked gene: PPP1R12A as ready
Intellectual disability syndromic and non-syndromic v0.1417 PPP1R12A Zornitza Stark gene: PPP1R12A was added
gene: PPP1R12A was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Research
Mode of inheritance for gene: PPP1R12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPP1R12A were set to Intellectual disability; holoprosencephaly; disorder of sex development
Added comment: Emerging evidence.
Sources: Research
Intellectual disability syndromic and non-syndromic v0.1416 ANKRD17 Zornitza Stark Marked gene: ANKRD17 as ready
Intellectual disability syndromic and non-syndromic v0.1415 ANKRD17 Zornitza Stark gene: ANKRD17 was added
gene: ANKRD17 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Research
Mode of inheritance for gene: ANKRD17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ANKRD17 were set to Intellectual disability; dysmorphic features
Review for gene: ANKRD17 was set to AMBER
Added comment: Emerging evidence.
Sources: Research
Intellectual disability syndromic and non-syndromic v0.1414 ZFHX3 Zornitza Stark Marked gene: ZFHX3 as ready
Intellectual disability syndromic and non-syndromic v0.1414 ZFHX3 Zornitza Stark Added comment: Comment when marking as ready: Emerging evidence.
Intellectual disability syndromic and non-syndromic v0.1414 ZFHX3 Zornitza Stark changed review comment from: Personal communication: Over 20 individuals with mostly de novo variants in this gene and mild ID/DD
Sources: Research; to: Emerging evidence.
Sources: Research
Intellectual disability syndromic and non-syndromic v0.1413 ZFHX3 Zornitza Stark Marked gene: ZFHX3 as ready
Intellectual disability syndromic and non-syndromic v0.1412 ZFHX3 Zornitza Stark gene: ZFHX3 was added
gene: ZFHX3 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Research
Mode of inheritance for gene: ZFHX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ZFHX3 were set to Intellectual disability
Review for gene: ZFHX3 was set to GREEN
Added comment: Personal communication: Over 20 individuals with mostly de novo variants in this gene and mild ID/DD
Sources: Research
Intellectual disability syndromic and non-syndromic v0.1411 USP7 Natasha Brown Marked gene: USP7 as ready
Intellectual disability syndromic and non-syndromic v0.1409 SEC31A Tiong Tan Marked gene: SEC31A as ready
Intellectual disability syndromic and non-syndromic v0.1407 SLC12A2 Zornitza Stark Marked gene: SLC12A2 as ready
Intellectual disability syndromic and non-syndromic v0.1405 POLD2 Zornitza Stark Marked gene: POLD2 as ready
Intellectual disability syndromic and non-syndromic v0.1404 POLD1 Zornitza Stark Marked gene: POLD1 as ready
Intellectual disability syndromic and non-syndromic v0.1404 POLD1 Zornitza Stark gene: POLD1 was added
gene: POLD1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: POLD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLD1 were set to 31449058
Phenotypes for gene: POLD1 were set to Intellectual disability; immunodeficiency
Review for gene: POLD1 was set to RED
Added comment: Single family reported with biallelic variants in this gene. Note heterozygous variants cause a different condition: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM#615381
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1403 ZNF292 Zornitza Stark Marked gene: ZNF292 as ready
Intellectual disability syndromic and non-syndromic v0.1402 ZMIZ1 Zornitza Stark Marked gene: ZMIZ1 as ready
Intellectual disability syndromic and non-syndromic v0.1402 ZMIZ1 Zornitza Stark Added comment: Comment when marking as ready: Please note transcription error in review relating to another gene, ZNF292. 19 families reported with heterozygous variants in this gene and a neurodevelopmental phenotype.
Intellectual disability syndromic and non-syndromic v0.1402 VAMP2 Zornitza Stark Marked gene: VAMP2 as ready
Intellectual disability syndromic and non-syndromic v0.1401 TUBB Zornitza Stark Marked gene: TUBB as ready
Intellectual disability syndromic and non-syndromic v0.1398 TENM3 Zornitza Stark Marked gene: TENM3 as ready
Intellectual disability syndromic and non-syndromic v0.1398 TENM3 Zornitza Stark Added comment: Comment when marking as ready: Intellectual disability is part of the phenotype.
Intellectual disability syndromic and non-syndromic v0.1397 TENM3 Zornitza Stark gene: TENM3 was added
gene: TENM3 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: TENM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TENM3 were set to 30513139; 22766609; 27103084; 29753094
Phenotypes for gene: TENM3 were set to Microphthalmia, syndromic 15, MIM#615145; coloboma
Review for gene: TENM3 was set to GREEN
Added comment: At least four unrelated families described with syndromic microphthalmia and bi-allelic variants in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1396 TARS Zornitza Stark Marked gene: TARS as ready
Intellectual disability syndromic and non-syndromic v0.1396 TARS Zornitza Stark Gene: tars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.1396 SNRPE Zornitza Stark Marked gene: SNRPE as ready
Intellectual disability syndromic and non-syndromic v0.1396 SNRPE Zornitza Stark Added comment: Comment when marking as ready: Three unrelated families reported with hypotrichosis simplex; only one family reported with ID.
Intellectual disability syndromic and non-syndromic v0.1395 SCAMP5 Zornitza Stark Marked gene: SCAMP5 as ready
Intellectual disability syndromic and non-syndromic v0.1395 SCAMP5 Zornitza Stark Added comment: Comment when marking as ready: Two unrelated individuals and functional data, upgraded to Green.
Intellectual disability syndromic and non-syndromic v0.1394 PISD Zornitza Stark Phenotypes for gene: PISD were changed from no OMIM number yet. to Intellectual disability; cataracts; retinal degeneration; microcephaly; deafness; short stature; white matter abnormalities; no OMIM number yet.
Intellectual disability syndromic and non-syndromic v0.1393 POLR2A Sue White Marked gene: POLR2A as ready
Intellectual disability syndromic and non-syndromic v0.1392 POLR2A Sue White gene: POLR2A was added
gene: POLR2A was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2A were set to 31353023
Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, MIM# 618603
Mode of pathogenicity for gene: POLR2A was set to Other
Review for gene: POLR2A was set to GREEN
Added comment: 11 unrelated individuals reported with de novo variants in this gene. Missense variants postulated to exert a dominant-negative effect; LoF variants by contrast resulted in milder phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1391 GNAI1 Zornitza Stark Marked gene: GNAI1 as ready
Intellectual disability syndromic and non-syndromic v0.1388 NLGN1 Zornitza Stark Marked gene: NLGN1 as ready
Intellectual disability syndromic and non-syndromic v0.1387 NCAPD2 Zornitza Stark Marked gene: NCAPD2 as ready
Intellectual disability syndromic and non-syndromic v0.1387 NCAPD2 Zornitza Stark Added comment: Comment when marking as ready: Three families, upgraded to Green.
Intellectual disability syndromic and non-syndromic v0.1386 MEPCE Zornitza Stark Marked gene: MEPCE as ready
Intellectual disability syndromic and non-syndromic v0.1385 LMAN2L Zornitza Stark Marked gene: LMAN2L as ready
Intellectual disability syndromic and non-syndromic v0.1384 GTF2E2 Zornitza Stark Marked gene: GTF2E2 as ready
Intellectual disability syndromic and non-syndromic v0.1384 GTF2E2 Zornitza Stark Added comment: Comment when marking as ready: Two unrelated families with functional data, upgrade to Green.
Intellectual disability syndromic and non-syndromic v0.1383 ADGRG6 Zornitza Stark Marked gene: ADGRG6 as ready
Intellectual disability syndromic and non-syndromic v0.1383 FRY Zornitza Stark Marked gene: FRY as ready
Intellectual disability syndromic and non-syndromic v0.1382 FBXL3 Zornitza Stark Marked gene: FBXL3 as ready
Intellectual disability syndromic and non-syndromic v0.1382 FBXL3 Zornitza Stark Added comment: Comment when marking as ready: Three families, all different variants, promote to green.
Intellectual disability syndromic and non-syndromic v0.1379 ETS1 Zornitza Stark Marked gene: ETS1 as ready
Intellectual disability syndromic and non-syndromic v0.1379 ETS1 Zornitza Stark gene: ETS1 was added
gene: ETS1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: ETS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ETS1 were set to 31160359
Phenotypes for gene: ETS1 were set to Intellectual disability
Review for gene: ETS1 was set to RED
Added comment: Single individual with de novo truncating variant in this gene; gene is Jacobsen syndrome critical region.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1378 ELMOD1 Zornitza Stark Marked gene: ELMOD1 as ready
Intellectual disability syndromic and non-syndromic v0.1377 EEF1D Zornitza Stark Marked gene: EEF1D as ready
Intellectual disability syndromic and non-syndromic v0.1376 EEF1D Zornitza Stark gene: EEF1D was added
gene: EEF1D was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: EEF1D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEF1D were set to 30787422; 28097321
Phenotypes for gene: EEF1D were set to Intellectual disability
Review for gene: EEF1D was set to AMBER
Added comment: Two unrelated families reported; one as part of a very large cohort of consanguineous families reporting multiple new candidate genes. No functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1375 DYNC1I2 Zornitza Stark Marked gene: DYNC1I2 as ready
Intellectual disability syndromic and non-syndromic v0.1373 DTYMK Zornitza Stark Marked gene: DTYMK as ready
Intellectual disability syndromic and non-syndromic v0.1373 DTYMK Zornitza Stark gene: DTYMK was added
gene: DTYMK was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: DTYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DTYMK were set to 31271740
Phenotypes for gene: DTYMK were set to Intellectual disability; microcephaly
Review for gene: DTYMK was set to RED
Added comment: Single family, two affected sibs with compound het variants reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1372 DNAJA1 Zornitza Stark Marked gene: DNAJA1 as ready
Intellectual disability syndromic and non-syndromic v0.1372 DNAJA1 Zornitza Stark gene: DNAJA1 was added
gene: DNAJA1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: DNAJA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJA1 were set to 30972502
Phenotypes for gene: DNAJA1 were set to Intellectual disability; seizures
Review for gene: DNAJA1 was set to RED
Added comment: Single family with multiple affected individuals reported with bi-allelic truncating variant in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1371 DLL1 Zornitza Stark Marked gene: DLL1 as ready
Intellectual disability syndromic and non-syndromic v0.1370 DLL1 Zornitza Stark gene: DLL1 was added
gene: DLL1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: DLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLL1 were set to 31353024
Phenotypes for gene: DLL1 were set to Intellectual disability; autism; seizures; variable brain abnormalities; scoliosis
Review for gene: DLL1 was set to GREEN
Added comment: Fifteen individuals from 12 unrelated families reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1369 DDX6 Zornitza Stark Marked gene: DDX6 as ready
Intellectual disability syndromic and non-syndromic v0.1368 DDX6 Zornitza Stark gene: DDX6 was added
gene: DDX6 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: DDX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX6 were set to 31422817,
Phenotypes for gene: DDX6 were set to Intellectual developmental disorder with impaired language and dysmorphic facies, MIM#618653
Review for gene: DDX6 was set to GREEN
Added comment: Five unrelated individuals reported with 5 different de novo heterozygous missense mutations in exon 11 of the DDX6 gene. All variants occurred at conserved residues in either the QxxR or V motifs within the second RecA-2 domain of the helicase core; this region is involved in RNA and/or ATP binding, suggesting functional consequences.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1367 CYFIP2 Zornitza Stark Marked gene: CYFIP2 as ready
Intellectual disability syndromic and non-syndromic v0.1366 CYFIP2 Zornitza Stark gene: CYFIP2 was added
gene: CYFIP2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: CYFIP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYFIP2 were set to 29534297
Phenotypes for gene: CYFIP2 were set to Epileptic encephalopathy, early infantile, 65, MIM#618008
Review for gene: CYFIP2 was set to GREEN
Added comment: Four unrelated individuals with de novo variants in this gene. All variants affected the same highly conserved residue (arg87) in the DUF1394 domain.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1365 CSDE1 Zornitza Stark Marked gene: CSDE1 as ready
Intellectual disability syndromic and non-syndromic v0.1364 CSDE1 Zornitza Stark gene: CSDE1 was added
gene: CSDE1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: CSDE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CSDE1 were set to 31579823
Phenotypes for gene: CSDE1 were set to Autism; intellectual disability; seizures; macrocephaly
Review for gene: CSDE1 was set to GREEN
Added comment: 18 families reported with high impact (stoppage/frameshift) variants in this gene. Eight de novo, eight inherited, two with undetermined inheritance. Functional data. Parents who had the variants were also affected, though generally more mildly.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1363 FAM160B1 Chirag Patel gene: FAM160B1 was added
gene: FAM160B1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: FAM160B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM160B1 were set to PMID: 31353455; 27431290
Phenotypes for gene: FAM160B1 were set to no OMIM number yet
Review for gene: FAM160B1 was set to RED
Added comment: 1 patient with severe ID, microcephaly, behavioral abnormalities, speech problems, mild ataxia and mild facial dysmorphism, and homozygous truncating variant in FAM160B1. No functional studies.

1 family with 2 sibs with DD, ID, speech issues, and with homozygous missense variant in FAM160B1. No functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1363 FAM160B1 Chirag Patel gene: FAM160B1 was added
gene: FAM160B1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: FAM160B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM160B1 were set to PMID: 31353455; 27431290
Phenotypes for gene: FAM160B1 were set to no OMIM number yet
Review for gene: FAM160B1 was set to RED
Added comment: 1 patient with severe ID, microcephaly, behavioral abnormalities, speech problems, mild ataxia and mild facial dysmorphism, and homozygous truncating variant in FAM160B1. No functional studies.

1 family with 2 sibs with DD, ID, speech issues, and with homozygous missense variant in FAM160B1. No functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1361 FBXL3 Chirag Patel gene: FBXL3 was added
gene: FBXL3 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: FBXL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXL3 were set to PubMed: 30481285
Phenotypes for gene: FBXL3 were set to Intellectual developmental disorder with short stature, facial anomalies, and speech defects; OMIM #606220
Review for gene: FBXL3 was set to AMBER
Added comment: 3 unrelated families with 8 affected individuals with ID, DD, short stature and mild facial dysmorphism, and with homozygous mutations in FBXL3. Segregated with the disorder in all 3 families. Functional studies of the variants and studies of patient cells were not performed.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1360 CNTN6 Zornitza Stark Marked gene: CNTN6 as ready
Intellectual disability syndromic and non-syndromic v0.1358 FRY Chirag Patel gene: FRY was added
gene: FRY was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: FRY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRY were set to PMID: 31487712; 27457812; 21937992
Phenotypes for gene: FRY were set to no OMIM number yet
Review for gene: FRY was set to AMBER
Added comment: 1 patient with ID/DD and a novel homozygous deletion involving FRY gene identified by genomic SNP microarray. No functional evidence.

2 consanguineous families with 6 affected individuals with ID, and homozygous mutations of FRY. No functional evidence.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1357 CMAS Zornitza Stark Marked gene: CMAS as ready
Intellectual disability syndromic and non-syndromic v0.1356 GABRA5 Chirag Patel Marked gene: GABRA5 as ready
Intellectual disability syndromic and non-syndromic v0.1355 GABRA5 Chirag Patel gene: GABRA5 was added
gene: GABRA5 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: GABRA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA5 were set to PMID: 31056671; 29961870
Phenotypes for gene: GABRA5 were set to Epileptic encephalopathy, early infantile, 79; OMIM #618559
Review for gene: GABRA5 was set to GREEN
Added comment: 3 unrelated patients with de novo heterozygous missense mutations in GABRA5 gene. In vitro functional expression studies in HEK293 cells showed that the mutant subunit was expressed at the surface and incorporated into the channel, but the mutant channel was 10 times more sensitive to GABA compared to wildtype. This increased sensitization resulted in increased receptor desensitization to GABA, with a reduced maximal GABA-evoked current and impaired capacity to pass GABAergic chloride current.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1354 ADGRG6 Chirag Patel gene: ADGRG6 was added
gene: ADGRG6 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: ADGRG6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGRG6 were set to PMID: 30549416
Phenotypes for gene: ADGRG6 were set to Lethal congenital contracture syndrome 9; OMIM #616503
Review for gene: ADGRG6 was set to RED
Added comment: 1 family with 2 patients with profound ID, severe speech impairment, microcephaly, seizures, spasticity, and cerebellar hypoplasia, with homozygous missense variation in ADGRG6 (GPR126). No functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1353 CDK8 Zornitza Stark Marked gene: CDK8 as ready
Intellectual disability syndromic and non-syndromic v0.1352 CDK8 Zornitza Stark gene: CDK8 was added
gene: CDK8 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: CDK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK8 were set to 30905399
Phenotypes for gene: CDK8 were set to Intellectual disability; dysmorphism; congenital abnormalities; seizures
Review for gene: CDK8 was set to GREEN
Added comment: 12 unrelated individuals, missense variants demonstrated as de novo in 10. All variants localize to the ATP-binding pocket of the kinase domain.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1351 GRIA2 Chirag Patel Marked gene: GRIA2 as ready
Intellectual disability syndromic and non-syndromic v0.1350 GRIA2 Chirag Patel gene: GRIA2 was added
gene: GRIA2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: GRIA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIA2 were set to PMID: 31300657
Phenotypes for gene: GRIA2 were set to no OMIM number yet
Review for gene: GRIA2 was set to GREEN
Added comment: 28 unrelated patients with ID, ASD, Rett-like features, seizures/EE, and de novo heterozygous GRIA2 mutations. In functional expression studies, mutations led to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1349 GTF2E2 Chirag Patel changed review comment from: 2 unrelated non-photosensitive TTD families with homozygous missense mutation in GTF2E2. Functional evidence showing mutant TFIIEβ strongly reduces the total amount of the entire TFIIE complex, with a remarkable temperature-sensitive transcription defect, which strikingly correlates with the phenotypic aggravation of key clinical symptoms after episodes of high fever. Induced pluripotent stem cell reprogramming of patient fibroblasts followed by in vitro erythroid differentiation, showed a clear hematopoietic defect during late-stage differentiation associated with hemoglobin subunit imbalance.
Sources: Literature; to: 2 unrelated non-photosensitive TTD families (3 affected) with homozygous missense mutation in GTF2E2. Functional evidence showing mutant TFIIEβ strongly reduces the total amount of the entire TFIIE complex, with a remarkable temperature-sensitive transcription defect, which strikingly correlates with the phenotypic aggravation of key clinical symptoms after episodes of high fever. Induced pluripotent stem cell reprogramming of patient fibroblasts followed by in vitro erythroid differentiation, showed a clear hematopoietic defect during late-stage differentiation associated with hemoglobin subunit imbalance.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1348 GTF2E2 Chirag Patel gene: GTF2E2 was added
gene: GTF2E2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: GTF2E2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF2E2 were set to PMID: 28973399
Phenotypes for gene: GTF2E2 were set to Trichothiodystrophy 6, nonphotosensitive; OMIM #616943
Review for gene: GTF2E2 was set to AMBER
Added comment: 2 unrelated non-photosensitive TTD families with homozygous missense mutation in GTF2E2. Functional evidence showing mutant TFIIEβ strongly reduces the total amount of the entire TFIIE complex, with a remarkable temperature-sensitive transcription defect, which strikingly correlates with the phenotypic aggravation of key clinical symptoms after episodes of high fever. Induced pluripotent stem cell reprogramming of patient fibroblasts followed by in vitro erythroid differentiation, showed a clear hematopoietic defect during late-stage differentiation associated with hemoglobin subunit imbalance.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1347 KDM3B Chirag Patel Marked gene: KDM3B as ready
Intellectual disability syndromic and non-syndromic v0.1346 KDM3B Chirag Patel gene: KDM3B was added
gene: KDM3B was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM3B were set to PMID: 30929739
Phenotypes for gene: KDM3B were set to no OMIM number yet
Review for gene: KDM3B was set to GREEN
Added comment: 14 unrelated individuals and 3 affected parents with varying degrees of ID, DD, short stature, dysmorphism, and de novo or inherited pathogenic variants in KDM3B. No functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1344 LMAN2L Chirag Patel gene: LMAN2L was added
gene: LMAN2L was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: LMAN2L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LMAN2L were set to PMID: 31020005; 26566883
Phenotypes for gene: LMAN2L were set to ?Mental retardation, autosomal recessive, 52; OMIM #616887
Review for gene: LMAN2L was set to AMBER
Added comment: 1 consanguineous family with 7 individuals with ID and epilepsy, with homozygous LMAN2L missense mutation. Segregated with disease in family, and unaffected family members were heterozygous variant carriers. No functional studies.

1 non-consanguineous family with 4 affected with heterozygous frameshift LMAN2L mutation. Segregates in family. Mutation eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1343 LSM1 Chirag Patel gene: LSM1 was added
gene: LSM1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: LSM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM1 were set to PMID: 31010896
Phenotypes for gene: LSM1 were set to no OMIM number yet
Review for gene: LSM1 was set to RED
Added comment: 1 family with 2 siblings with global DD, multiple congenital anomalies, and abnormal eye movements, with homozygous splice variant in LSM1. Segregated with the phenotype in the family. Expression studies revealed absence of expression of the canonical isoform in the affected individuals. The Lsm1 knockout mice have a partially overlapping phenotype that affects the brain, heart, and eye.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1342 LSS Chirag Patel Marked gene: LSS as ready
Intellectual disability syndromic and non-syndromic v0.1341 LSS Chirag Patel gene: LSS was added
gene: LSS was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSS were set to PMID: 30723320
Phenotypes for gene: LSS were set to Cataract 44, OMIM #616509; Hypotrichosis 14, OMIM #618275
Review for gene: LSS was set to GREEN
Added comment: Expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. Ten APMR individuals from 6 unrelated families with biallelic variants in LSS. Quantification of cholesterol and its precursors did not reveal noticeable imbalance.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1340 MACROD2 Chirag Patel gene: MACROD2 was added
gene: MACROD2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: MACROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MACROD2 were set to PMID: 31055587
Phenotypes for gene: MACROD2 were set to no OMIM number yet
Review for gene: MACROD2 was set to RED
Added comment: 1 family with a few affected with microcephaly, ID, dysmorphic features, and polydactyly. Deletion of chromosome 20p12.1 involving the MACROD2 gene was found in several members of the family. qRT-PCR showed higher levels of a MACROD2 mRNA isoform in the individuals carrying the deletion.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1339 MAST1 Chirag Patel Marked gene: MAST1 as ready
Intellectual disability syndromic and non-syndromic v0.1338 MAST1 Chirag Patel gene: MAST1 was added
gene: MAST1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to PMID: 31721002; 30449657
Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; OMIM #618273
Review for gene: MAST1 was set to GREEN
Added comment: 6 unrelated patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM) with de novo heterozygous mutations in MAST1 gene. In vitro functional studies showed that 1 of the variants (lys276del) increased MAST1 binding to microtubules compared to controls. Mutant mice heterozygous for a Mast1 leu278del allele showed a thicker corpus callosum compared to wildtype, and an overall reduction in cortical volume and thickness and decreased cerebellar volume and number of granule and Purkinje cells due to increased apoptosis compared to controls.

1 Emirati patient with ID, microcephaly, and dysmorphic features, with missense variant in MAST1.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1337 MEPCE Chirag Patel gene: MEPCE was added
gene: MEPCE was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: MEPCE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEPCE were set to PMID: 31467394
Phenotypes for gene: MEPCE were set to no OMIM number yet
Review for gene: MEPCE was set to RED
Added comment: 1 patient with global DD and seizures with de novo MEPCE nonsense variant. mRNA and protein analyses identified nonsense-mediated mRNA decay to underlie the decreased amount of MEPCE in patient fibroblasts followed by LARP7 and 7SK snRNA downregulation and HEXIM1 upregulation. Flavopiridol treatment and ectopic MEPCE protein expression in patient fibroblasts rescued increased expression of six RNAP II-sensitive genes and suggested a possible repressive effect of MEPCE on P-TEFb-dependent transcription of specific genes.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1335 NCAPD2 Chirag Patel gene: NCAPD2 was added
gene: NCAPD2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: NCAPD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCAPD2 were set to PMID: 31056748; 27737959; 28097321
Phenotypes for gene: NCAPD2 were set to ?Microcephaly 21, primary, autosomal recessive; OMIM #617983
Review for gene: NCAPD2 was set to AMBER
Added comment: 1 family with 2 sibs with microcephaly and ID, and homozygous NCAPD2 mutation, which segregated with disease. No functional evidence.

1 family with 1 affected and homozygous NCAPD2 mutation, which segregated with disease. Patient fibroblasts showed impaired chromosome segregation and abnormal recovery from mitotic condensation compared to controls.

1 family with 2 sibs with microcephaly, growth retardation, and ID, and homozygous NCAPD2 mutation, which segregated with disease. Functional studies of the variants and studies of patient cells were not performed.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1334 NFASC Chirag Patel Marked gene: NFASC as ready
Intellectual disability syndromic and non-syndromic v0.1333 NFASC Chirag Patel gene: NFASC was added
gene: NFASC was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: NFASC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFASC were set to PMID: 31501903; 28940097; 30124836; 30850329; 31608123
Phenotypes for gene: NFASC were set to Neurodevelopmental disorder with central and peripheral motor dysfunction; OMIM #618356
Review for gene: NFASC was set to GREEN
Added comment: > 10 unrelated families reported, exhibiting a neurodevelopmental disorder (intellectual disability, developmental delay, motor impairment, speech difficulties, early onset demyelinating neuropathy), with homozygous variants in NFASC. Segregated with the disorder in the family. Some studies with functional evidence.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1332 NLGN1 Chirag Patel gene: NLGN1 was added
gene: NLGN1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: NLGN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NLGN1 were set to PMID: 30460678
Phenotypes for gene: NLGN1 were set to no OMIM number yet
Review for gene: NLGN1 was set to RED
Added comment: homozygous variant in the NLGN1 gene found in a pair of monozygotic twin brothers with intellectual disability and autism. Segregated with disease. No functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1331 P4HTM Chirag Patel Marked gene: P4HTM as ready
Intellectual disability syndromic and non-syndromic v0.1330 P4HTM Chirag Patel gene: P4HTM was added
gene: P4HTM was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: P4HTM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P4HTM were set to PMID: 25078763; 30940925
Phenotypes for gene: P4HTM were set to Hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities; OMIM #618493
Review for gene: P4HTM was set to GREEN
Added comment: 12 patients from 5 families with hypotonia, intellectual disability, and eye abnormalities, and homozygous or compound heterozygous pathogenic P4HTM gene variants. Segregated with the disorder in the families. In vitro functional expression studies of 3 of the P4HTM variants showed that they caused a significant decrease in the amount of soluble protein compared to wildtype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1329 PAK1 Chirag Patel Marked gene: PAK1 as ready
Intellectual disability syndromic and non-syndromic v0.1328 PAK1 Chirag Patel gene: PAK1 was added
gene: PAK1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK1 were set to PMID: 31504246; 30290153
Phenotypes for gene: PAK1 were set to Intellectual developmental disorder with macrocephaly, seizures, and speech delay; OMIM #618158
Review for gene: PAK1 was set to GREEN
Added comment: 2 unrelated individuals with de novo PAK1 mutations, with developmental delay, secondary macrocephaly, seizures, and ataxic gait. Enhanced phosphorylation of the PAK1 targets JNK and AKT shown in fibroblasts of one subject and of c-JUN in those of both subjects compared with control subjects. In fibroblasts of the 2 affected individuals, they observed a trend toward enhanced PAK1 kinase activity. By using co-immunoprecipitation and size-exclusion chromatography, they observed a significantly reduced dimerization for both PAK1 mutants compared with wild-type PAK1.

4 unrelated individuals with intellectual disability, macrocephaly and seizures, with de novo heterozygous missense variants in PAK1.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1327 PHF21A Chirag Patel Marked gene: PHF21A as ready
Intellectual disability syndromic and non-syndromic v0.1326 PHF21A Chirag Patel gene: PHF21A was added
gene: PHF21A was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PHF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF21A were set to PMID: 31649809; 30487643; 22770980
Phenotypes for gene: PHF21A were set to no OMIM number yet.
Review for gene: PHF21A was set to GREEN
Added comment: 9 cases with intellectual disability and craniofacial anomalies (Potocki-Shaffer syndrome), with de novo truncating variants in PHF21A. No functional evidence of variants, but PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype.

2 other unrelated individuals with translocations disrupting PHF21A. Lymphoblastoid cell lines from translocation subjects showed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional regulation.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1325 PIBF1 Chirag Patel Marked gene: PIBF1 as ready
Intellectual disability syndromic and non-syndromic v0.1324 PIBF1 Chirag Patel gene: PIBF1 was added
gene: PIBF1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to PubMed: 26167768; 30858804; 29695797
Phenotypes for gene: PIBF1 were set to Joubert syndrome 33; OMIM #617767
Review for gene: PIBF1 was set to GREEN
Added comment: 1 family of Schmiedeleut Hutterite descent with 2 affected brothers with Joubert syndrome had homozygous missense mutation in PIBF1 gene. Parents were heterozygous.

2 other Hutterite families with 3 affected children and same homozygous missense mutation in PIBF1 gene, suggesting a founder effect.

2 other unrelated individuals with compound heterozygous mutations in PIBF1 gene.

1 unrelated individual with compound heterozygous variants in PIBF1 gene, and functional evidence in the frog Xenopus.

1 unrelated individual with another homozygous missense mutation in PIBF1 gene, but no and functional evidence.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1323 PIGB Chirag Patel Marked gene: PIGB as ready
Intellectual disability syndromic and non-syndromic v0.1322 PIGB Chirag Patel gene: PIGB was added
gene: PIGB was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PIGB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGB were set to PubMed: 31256876
Phenotypes for gene: PIGB were set to Epileptic encephalopathy, early infantile, 80; OMIM #618580
Review for gene: PIGB was set to GREEN
Added comment: 10 unrelated families with biallelic mutations in PIGB, with global DD and/or ID, and seizures. Two had polymicrogyria, 4 had a peripheral neuropathy, and 2 had a clinical diagnosis of DOORS syndrome. Patient lymphocytes and fibroblasts showed variably decreased levels of cell surface GPI-anchored proteins, including CD16 and CD59. In vitro functional expression studies performed with some of the mutations in PIGB-null CHO cells showed that the mutant proteins were unable to fully restore expression of GPI-anchored surface proteins, consistent with a loss of function, although the mutations had variable effects.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1321 PIGU Chirag Patel Marked gene: PIGU as ready
Intellectual disability syndromic and non-syndromic v0.1320 PIGU Chirag Patel gene: PIGU was added
gene: PIGU was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PIGU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGU were set to PMID: 31353022
Phenotypes for gene: PIGU were set to Glycosylphosphatidylinositol biosynthesis defect 21; OMIM #618590
Review for gene: PIGU was set to GREEN
Added comment: 5 patients from 3 unrelated families, with homozygous missense mutations in the PIGU gene. All individuals presented with global DD, severe-to-profound ID, muscular hypotonia, seizures, brain anomalies, scoliosis, and mild facial dysmorphism. Flow cytometric analysis of patient granulocytes showed a characteristic pattern, with reduced cell surface expression of CD16 and CD24. In addition, patient B cells showed increased expression of free GPI anchors determined by a specific antibody, T5. The findings suggested that PIGU mutations reduce the function of the GPI transamidase complex, leading to accumulation of free GPI anchors on the cell surface.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1319 PISD Chirag Patel Marked gene: PISD as ready
Intellectual disability syndromic and non-syndromic v0.1317 PISD Chirag Patel changed review comment from: 4 individuals in 2 unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature (Liberfarb syndrome). Affected individuals shared a homozygous 10-bp deletion immediately upstream of the last exon of the PISD gene. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts.
Sources: Literature; to: 4 individuals in 2 unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature (Liberfarb syndrome). Affected individuals shared a homozygous 10-bp deletion immediately upstream of the last exon of the PISD gene. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts.

1 family with 2 sisters with congenital cataracts, short stature, and white matter changes identified compound heterozygous variants in the PISD gene. Decreased conversion of phosphatidylserine to PE in patient fibroblasts is consistent with impaired phosphatidylserine decarboxylase (PISD) enzyme activity.
Intellectual disability syndromic and non-syndromic v0.1317 PISD Chirag Patel gene: PISD was added
gene: PISD was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PISD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PISD were set to PMID: 31263216
Phenotypes for gene: PISD were set to no OMIM number yet.
Review for gene: PISD was set to AMBER
Added comment: 4 individuals in 2 unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature (Liberfarb syndrome). Affected individuals shared a homozygous 10-bp deletion immediately upstream of the last exon of the PISD gene. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1316 POU3F3 Chirag Patel Marked gene: POU3F3 as ready
Intellectual disability syndromic and non-syndromic v0.1315 POU3F3 Chirag Patel gene: POU3F3 was added
gene: POU3F3 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: POU3F3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU3F3 were set to PMID: 24550763; 31303265
Phenotypes for gene: POU3F3 were set to no OMIM number yet.
Review for gene: POU3F3 was set to GREEN
Added comment: 19 individuals with DD/ID/speech issues and heterozygous POU3F3 disruptions, most of which were de novo variants. Positive functional cell-based analyses of pathogenic variants.

1 patient reported with whole gene deletion and ID.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1313 PPP2CA Chirag Patel gene: PPP2CA was added
gene: PPP2CA was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PPP2CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2CA were set to PMID: 30595372
Phenotypes for gene: PPP2CA were set to Neurodevelopmental disorder and language delay with or without structural brain abnormalities; OMIM #618354
Review for gene: PPP2CA was set to GREEN
Added comment: 15 unrelated patients with a neurodevelopmental disorder with de novo heterozygous PPP2CA mutations, and 1 with partial deletion of PPP2CA. Functional studies showed complete PP2A dysfunction in 4 individuals with seemingly milder ID, hinting at haploinsufficiency. Ten other individuals showed mutation-specific biochemical distortions, including poor expression, altered binding to the A subunit and specific B-type subunits, and impaired phosphatase activity and C-terminal methylation.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1312 RNF113A Zornitza Stark Marked gene: RNF113A as ready
Intellectual disability syndromic and non-syndromic v0.1312 PUS7 Zornitza Stark Marked gene: PUS7 as ready
Intellectual disability syndromic and non-syndromic v0.1311 PUS7 Chirag Patel gene: PUS7 was added
gene: PUS7 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS7 were set to PMID: 30526862; 30778726; 31583274
Phenotypes for gene: PUS7 were set to Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature; OMIM #618342
Review for gene: PUS7 was set to GREEN
Added comment: 11 patients from 6 families with ID, speech delay, short stature, microcephaly, and aggressive behavior, with homozygous PUS7 mutations, which segregated with disease.

One study showed disease-related variants lead to abolishment of PUS7 activity on both tRNA and mRNA substrates. pus7 knockout in Drosophila melanogaster results in a number of behavioral defects, including increased activity, disorientation, and aggressiveness supporting that neurological defects are caused by PUS7 variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1309 RNF113A Chirag Patel gene: RNF113A was added
gene: RNF113A was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: RNF113A 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: RNF113A were set to PMID: 25612912; 31793730
Phenotypes for gene: RNF113A were set to ?Trichothiodystrophy 5, nonphotosensitive; OMIM #300953
Review for gene: RNF113A was set to AMBER
Added comment: 1 family of 2 male cousins with IUGR, progressive microcephaly, profound ID, genital anomalies, and severe linear growth failure, and nonsense Q301X mutation in RNF113A gene. Segregated with disease in the family. The mutation markedly reduced RNF113A protein expression in extracts from lymphoblastoid cell lines derived from the affected individuals.

2 fetuses affected with abnormalities similar to previous report, with the same nonsense Q301X mutation in RNF113A gene (can not access paper to see if from same family or functional evidence).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1307 SCAMP5 Chirag Patel gene: SCAMP5 was added
gene: SCAMP5 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: SCAMP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCAMP5 were set to PMID: 31439720
Phenotypes for gene: SCAMP5 were set to no OMIM number yet
Review for gene: SCAMP5 was set to AMBER
Added comment: 2 unrelated individuals with ASD, ID and seizures, with the same heterozygous de novo variant in SCAMP5 (p.Gly302Trp). Western blot analysis of proteins overexpressed in the Drosophila fat body showed strongly reduced levels of the SCAMP p.Gly302Trp protein compared with the wild-type protein, indicating that the mutant either reduced expression or increased turnover of the protein. The expression of the fly homologue of the human SCAMP5 p.Gly180Trp mutation caused similar eye and neuronal phenotypes as the expression of SCAMP RNAi, suggesting a dominant-negative effect.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1305 SCAPER Chirag Patel gene: SCAPER was added
gene: SCAPER was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: SCAPER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCAPER were set to PMID: 28794130; 31069901; 31192531; 30723319
Phenotypes for gene: SCAPER were set to Intellectual developmental disorder and retinitis pigmentosa; OMIM #618195
Review for gene: SCAPER was set to GREEN
Added comment: 28 patients from 14 unrelated families with ID and retinitis pigmentosa (some with BBS phenotype), and homozygous or compound heterozygous mutations in SCAPER gene. No functional evidence of specific variants.

Analyses of SCAPER expression in human and mouse brain revealed an upregulation of SCAPER expression during cortical development and a higher expression of SCAPER in neurons compared to neural progenitors.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1304 SMARCD1 Zornitza Stark Marked gene: SMARCD1 as ready
Intellectual disability syndromic and non-syndromic v0.1304 SMARCD1 Zornitza Stark Gene: smarcd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1304 SMARCC2 Zornitza Stark Marked gene: SMARCC2 as ready
Intellectual disability syndromic and non-syndromic v0.1304 SMARCC2 Zornitza Stark Gene: smarcc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1304 SEMA5A Zornitza Stark Marked gene: SEMA5A as ready
Intellectual disability syndromic and non-syndromic v0.1304 BRSK2 Zornitza Stark Marked gene: BRSK2 as ready
Intellectual disability syndromic and non-syndromic v0.1303 BRSK2 Zornitza Stark gene: BRSK2 was added
gene: BRSK2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: BRSK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRSK2 were set to 30879638
Phenotypes for gene: BRSK2 were set to Intellectual disability; autism
Review for gene: BRSK2 was set to GREEN
Added comment: Nine unrelated individuals with heterozygous variants in this gene; six confirmed de novo (parents available).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1301 SEMA5A Chirag Patel gene: SEMA5A was added
gene: SEMA5A was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: SEMA5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA5A were set to PMID: 26395558
Phenotypes for gene: SEMA5A were set to no OMIM number yet
Review for gene: SEMA5A was set to AMBER
Added comment: 1 patient with de novo translocation t(5;22)(p15.3;q11.21) and ASD and ID. At the translocation breakpoint on chromosome 5, they observed a 861-kb deletion encompassing the end of the SEMA5A gene. No functional studies.

2 patients with ASD and predicted deleterious heterozygous variants (maternally inherited). No functional studies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1300 BCORL1 Zornitza Stark Marked gene: BCORL1 as ready
Intellectual disability syndromic and non-syndromic v0.1299 SMARCC2 Chirag Patel Classified gene: SMARCC2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.1299 SMARCC2 Chirag Patel Gene: smarcc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1298 SMARCC2 Chirag Patel gene: SMARCC2 was added
gene: SMARCC2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: SMARCC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCC2 were set to PMID: 30580808
Phenotypes for gene: SMARCC2 were set to Coffin-Siris syndrome 8; OMIM #618362
Review for gene: SMARCC2 was set to GREEN
Added comment: 15 individuals with variable degrees of neurodevelopmental delay, growth retardation, prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features. They found heterozygous de novo SMARCC2 variants, but no functional evidence of specific variants. Transcriptomic analysis of fibroblasts from affected individuals highlighted a group of differentially expressed genes with possible roles in regulation of neuronal development and function, namely H19, SCRG1, RELN, and CACNB4.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1297 SMARCD1 Chirag Patel Classified gene: SMARCD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.1297 SMARCD1 Chirag Patel Gene: smarcd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1296 SMARCD1 Chirag Patel gene: SMARCD1 was added
gene: SMARCD1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: SMARCD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCD1 were set to PMID: 30879640
Phenotypes for gene: SMARCD1 were set to no OMIM number yet
Review for gene: SMARCD1 was set to GREEN
Added comment: 5 individuals with heterozygous SMARCD1 variants (4 de novo, 1 unk), and developmental delay, intellectual disability, hypotonia, feeding difficulties, dysmorphisms, and small hands and feet. No functional evidence of some variants was not conclusive with immunoblot or co-immunoprecipitation studies. Targeted knockdown of Drosophila ortholog Bap60 in the mushroom body of adult flies causes defects in long-term memory. Mushroom-body-specific transcriptome analysis revealed that Bap60 is required for context-dependent expression of genes involved in neuron function and development in juvenile flies when synaptic connections are actively being formed in response to experience. T
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1295 BCL11B Zornitza Stark Marked gene: BCL11B as ready
Intellectual disability syndromic and non-syndromic v0.1294 BCL11B Zornitza Stark gene: BCL11B was added
gene: BCL11B was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: BCL11B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BCL11B were set to 29985992
Phenotypes for gene: BCL11B were set to Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities, MIM# 618092
Review for gene: BCL11B was set to GREEN
Added comment: Nine unrelated individuals, all but one with de novo variants in this gene and syndromic ID/immunodeficiency. Most variants located in the last exon (exon 4) and are predicted to escape nonsense-mediated mRNA decay.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1293 SNRPE Chirag Patel gene: SNRPE was added
gene: SNRPE was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: SNRPE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SNRPE were set to Hypotrichosis 11; OMIM #615059
Review for gene: SNRPE was set to AMBER
Added comment: 1 patient with de novo heterozygous missense SNRPE mutation, with non-syndromic primary microcephaly and intellectual disability. SNRPE encodes SmE and they showed that the microcephaly-linked SmE variant is unable to interact with the SMN complex and as a consequence fails to assemble into U snRNPs. This results in widespread mRNA splicing alterations in fibroblast cells derived from this patient. Similar alterations were observed in HEK293 cells upon SmE depletion that could be rescued by the expression of wild type but not mutant SmE. Depletion of SmE in zebrafish causes aberrant mRNA splicing alterations and reduced brain size, reminiscent of the patient microcephaly phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1291 SOX4 Chirag Patel gene: SOX4 was added
gene: SOX4 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: SOX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX4 were set to PMID: 30661772
Phenotypes for gene: SOX4 were set to Coffin-Siris syndrome 10; OMIM #618506
Review for gene: SOX4 was set to GREEN
Added comment: 4 patients with syndromic DD/ID and de novo mutations in SOX4 gene. Functional assays demonstrated that the SOX4 proteins carrying these variants were unable to bind DNA in vitro and transactivate SOX reporter genes in cultured cells.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1289 SVBP Chirag Patel gene: SVBP was added
gene: SVBP was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SVBP were set to PMID: 31363758; 30607023
Phenotypes for gene: SVBP were set to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly; OMIM #618569
Review for gene: SVBP was set to GREEN
Added comment: 5 unrelated families with homozygous mutations in SVBP. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1287 TANC2 Chirag Patel gene: TANC2 was added
gene: TANC2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TANC2 were set to PMID: 31616000
Phenotypes for gene: TANC2 were set to no OMIM number yet
Review for gene: TANC2 was set to GREEN
Added comment: 19 families with potentially disruptive heterozygous TANC2 variants, including 16 likely gene-disrupting mutations and three intragenic microdeletions. Patients presented with autism, intellectual disability, delayed language and motor development, epilepsy, facial dysmorphism, with complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. No functional evidence of specific variants, but they show TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, and shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1286 ATN1 Zornitza Stark Marked gene: ATN1 as ready
Intellectual disability syndromic and non-syndromic v0.1285 ATN1 Zornitza Stark gene: ATN1 was added
gene: ATN1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: ATN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATN1 were set to 30827498
Phenotypes for gene: ATN1 were set to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies, MIM#618494
Review for gene: ATN1 was set to GREEN
Added comment: Eight unrelated individuals with de novo heterozygous variants in this gene and syndromic ID; all variants result in substitutions within the highly conserved 16-amino acid histidine-rich 'HX repeat' motif near the C terminus.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1284 TARS Chirag Patel Classified gene: TARS as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.1284 TARS Chirag Patel Gene: tars has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.1283 TARS Chirag Patel gene: TARS was added
gene: TARS was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: TARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TARS were set to PMID: 31374204
Phenotypes for gene: TARS were set to Trichothiodystrophy 7, nonphotosensitive; OMIM #618546
Review for gene: TARS was set to AMBER
Added comment: Clinical features of trichothiodystrophy (TTD) include ichthyosis, intellectual disability, decreased fertility, short stature.

2 unrelated patients with non-photosensitive-TTD, in whom limited clinical information was available (one with DD): one compound heterozygous TARS variants, second homozygous for TARS variant. They showed that the variants had a profound effect on TARS protein stability and enzymatic function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1282 TEMN3-AS1 Chirag Patel changed review comment from: 3 unrelated families, but no functional evidence.
Sources: Literature; to: 3 unrelated families with DD/ID as part of syndromic microphthalmia, but no functional evidence.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1280 APC2 Zornitza Stark Marked gene: APC2 as ready
Intellectual disability syndromic and non-syndromic v0.1277 VAMP2 Chirag Patel gene: VAMP2 was added
gene: VAMP2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: VAMP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VAMP2 were set to PMID: 30929742
Phenotypes for gene: VAMP2 were set to no OMIM number yet
Review for gene: VAMP2 was set to GREEN
Added comment: 5 unrelated patients with heterozygous de novo mutations in VAMP2, presenting with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1275 ZMIZ1 Chirag Patel gene: ZMIZ1 was added
gene: ZMIZ1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: ZMIZ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMIZ1 were set to PubMed: 30639322
Phenotypes for gene: ZMIZ1 were set to Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies; OMIM #618659
Review for gene: ZMIZ1 was set to GREEN
Added comment: 28 families with spectrum of neurodevelopmental features (including ID, ASD, and ADHD) due to de novo ZNF292 variants (1 family inherited). No functional evidence of specific variants, but ZNF292 is highly expressed in the developing human brain.


14 unrelated patients with neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies, and de novo heterozygous mutations in the ZMIZ1 gene. Transfection of 3 variants (T300M, c.3112dupA, and K91R) into HEK293T cells resulted in decreased induction of luciferase activity compared to wildtype (although the change for K91R was not statistically significant), suggesting impaired coactivation activity of the mutant proteins. Electroporation of these 3 mutants into progenitor cells in the ventricular zone of embryonic mice cortices resulted in defective neuronal migration to the cortex, as well as morphologic abnormalities of the neurons manifest as rounded cells with aberrantly oriented processes. These findings suggested that the ZMIZ1 mutations disrupted proper neuronal polarization and neuronal migration in the developing cortex. Functional studies of the other variants and additional studies of patient cells were not performed.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1273 ZNF292 Chirag Patel gene: ZNF292 was added
gene: ZNF292 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: ZNF292 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF292 were set to PMID: 31723249
Phenotypes for gene: ZNF292 were set to no OMIM number yet
Review for gene: ZNF292 was set to GREEN
Added comment: 28 families with spectrum of neurodevelopmental features (including ID, ASD, and ADHD) due to de novo ZNF292 variants (1 family inherited). No functional evidence of specific variants, but ZNF292 is highly expressed in the developing human brain.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1272 ALKBH8 Zornitza Stark Marked gene: ALKBH8 as ready
Intellectual disability syndromic and non-syndromic v0.1270 ADGRB3 Zornitza Stark Marked gene: ADGRB3 as ready
Intellectual disability syndromic and non-syndromic v0.1269 ACTL6B Zornitza Stark Marked gene: ACTL6B as ready
Intellectual disability syndromic and non-syndromic v0.1268 ACTL6B Zornitza Stark gene: ACTL6B was added
gene: ACTL6B was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: ACTL6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACTL6B were set to 31134736; 31031012; 30656450; 30237576
Phenotypes for gene: ACTL6B were set to Epileptic encephalopathy, early infantile, 76, MIM# 618468; Intellectual developmental disorder with severe speech and ambulation defects, MIM# 618470
Review for gene: ACTL6B was set to GREEN
Added comment: Multiple affected individuals reported, main phenotype is ID/EE.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1267 SP7 Zornitza Stark Marked gene: SP7 as ready
Intellectual disability syndromic and non-syndromic v0.1265 SPEG Zornitza Stark Marked gene: SPEG as ready
Intellectual disability syndromic and non-syndromic v0.1265 SPINK5 Zornitza Stark Marked gene: SPINK5 as ready
Intellectual disability syndromic and non-syndromic v0.1265 SPTLC1 Zornitza Stark Marked gene: SPTLC1 as ready
Intellectual disability syndromic and non-syndromic v0.1264 ST7 Zornitza Stark Marked gene: ST7 as ready
Intellectual disability syndromic and non-syndromic v0.1264 STAC3 Zornitza Stark Marked gene: STAC3 as ready
Intellectual disability syndromic and non-syndromic v0.1264 STAT5B Zornitza Stark Marked gene: STAT5B as ready
Intellectual disability syndromic and non-syndromic v0.1264 STK3 Zornitza Stark Marked gene: STK3 as ready
Intellectual disability syndromic and non-syndromic v0.1261 STT3A Zornitza Stark Marked gene: STT3A as ready
Intellectual disability syndromic and non-syndromic v0.1261 STT3B Zornitza Stark Marked gene: STT3B as ready
Intellectual disability syndromic and non-syndromic v0.1261 TAF8 Zornitza Stark Marked gene: TAF8 as ready
Intellectual disability syndromic and non-syndromic v0.1261 TDGF1 Zornitza Stark Marked gene: TDGF1 as ready
Intellectual disability syndromic and non-syndromic v0.1260 TFAP2A Zornitza Stark Marked gene: TFAP2A as ready
Intellectual disability syndromic and non-syndromic v0.1260 TFAP2B Zornitza Stark Marked gene: TFAP2B as ready
Intellectual disability syndromic and non-syndromic v0.1260 TFG Zornitza Stark Marked gene: TFG as ready
Intellectual disability syndromic and non-syndromic v0.1260 TG Zornitza Stark Marked gene: TG as ready
Intellectual disability syndromic and non-syndromic v0.1260 TGFBR1 Zornitza Stark Marked gene: TGFBR1 as ready
Intellectual disability syndromic and non-syndromic v0.1260 TGFBR2 Zornitza Stark Marked gene: TGFBR2 as ready
Intellectual disability syndromic and non-syndromic v0.1260 THAP1 Zornitza Stark Marked gene: THAP1 as ready
Intellectual disability syndromic and non-syndromic v0.1260 TIMM8A Zornitza Stark Marked gene: TIMM8A as ready
Intellectual disability syndromic and non-syndromic v0.1260 TNRC6B Zornitza Stark Marked gene: TNRC6B as ready
Intellectual disability syndromic and non-syndromic v0.1260 TP63 Zornitza Stark Marked gene: TP63 as ready
Intellectual disability syndromic and non-syndromic v0.1260 ERLIN2 Zornitza Stark Marked gene: ERLIN2 as ready
Intellectual disability syndromic and non-syndromic v0.1260 TRAPPC6A Zornitza Stark Marked gene: TRAPPC6A as ready
Intellectual disability syndromic and non-syndromic v0.1260 TREM2 Zornitza Stark Marked gene: TREM2 as ready
Intellectual disability syndromic and non-syndromic v0.1260 TRHR Zornitza Stark Marked gene: TRHR as ready
Intellectual disability syndromic and non-syndromic v0.1260 TRIM37 Zornitza Stark Marked gene: TRIM37 as ready
Intellectual disability syndromic and non-syndromic v0.1260 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Intellectual disability syndromic and non-syndromic v0.1260 TTR Zornitza Stark Marked gene: TTR as ready
Intellectual disability syndromic and non-syndromic v0.1260 TWNK Zornitza Stark Marked gene: TWNK as ready
Intellectual disability syndromic and non-syndromic v0.1260 UCHL1 Zornitza Stark Marked gene: UCHL1 as ready
Intellectual disability syndromic and non-syndromic v0.1260 UGT1A1 Zornitza Stark Marked gene: UGT1A1 as ready
Intellectual disability syndromic and non-syndromic v0.1260 UNC13D Zornitza Stark Marked gene: UNC13D as ready
Intellectual disability syndromic and non-syndromic v0.1260 UQCRB Zornitza Stark Marked gene: UQCRB as ready
Intellectual disability syndromic and non-syndromic v0.1260 UQCRC2 Zornitza Stark Marked gene: UQCRC2 as ready
Intellectual disability syndromic and non-syndromic v0.1260 UQCRQ Zornitza Stark Marked gene: UQCRQ as ready
Intellectual disability syndromic and non-syndromic v0.1260 VAMP1 Zornitza Stark Marked gene: VAMP1 as ready
Intellectual disability syndromic and non-syndromic v0.1259 VANGL1 Zornitza Stark Marked gene: VANGL1 as ready
Intellectual disability syndromic and non-syndromic v0.1259 VPS45 Zornitza Stark Marked gene: VPS45 as ready
Intellectual disability syndromic and non-syndromic v0.1259 WASHC4 Zornitza Stark Marked gene: WASHC4 as ready
Intellectual disability syndromic and non-syndromic v0.1259 WASHC5 Zornitza Stark Marked gene: WASHC5 as ready
Intellectual disability syndromic and non-syndromic v0.1259 WDR11 Zornitza Stark Marked gene: WDR11 as ready
Intellectual disability syndromic and non-syndromic v0.1259 WDR13 Zornitza Stark Marked gene: WDR13 as ready
Intellectual disability syndromic and non-syndromic v0.1259 WDR19 Zornitza Stark Marked gene: WDR19 as ready
Intellectual disability syndromic and non-syndromic v0.1259 WDR34 Zornitza Stark Marked gene: WDR34 as ready
Intellectual disability syndromic and non-syndromic v0.1259 WRAP53 Zornitza Stark Marked gene: WRAP53 as ready
Intellectual disability syndromic and non-syndromic v0.1259 ZCCHC12 Zornitza Stark Marked gene: ZCCHC12 as ready
Intellectual disability syndromic and non-syndromic v0.1259 ZDHHC15 Zornitza Stark Marked gene: ZDHHC15 as ready
Intellectual disability syndromic and non-syndromic v0.1259 ZFP57 Zornitza Stark Marked gene: ZFP57 as ready
Intellectual disability syndromic and non-syndromic v0.1259 ZMYM3 Zornitza Stark Marked gene: ZMYM3 as ready
Intellectual disability syndromic and non-syndromic v0.1258 ZNF41 Zornitza Stark Marked gene: ZNF41 as ready
Intellectual disability syndromic and non-syndromic v0.1257 ZNF423 Zornitza Stark Marked gene: ZNF423 as ready
Intellectual disability syndromic and non-syndromic v0.1257 ZNF507 Zornitza Stark Marked gene: ZNF507 as ready
Intellectual disability syndromic and non-syndromic v0.1257 ZNF674 Zornitza Stark Marked gene: ZNF674 as ready
Intellectual disability syndromic and non-syndromic v0.1256 ZNF804A Zornitza Stark Marked gene: ZNF804A as ready
Intellectual disability syndromic and non-syndromic v0.1256 ZNHIT6 Zornitza Stark Marked gene: ZNHIT6 as ready
Intellectual disability syndromic and non-syndromic v0.1256 MEGF8 Zornitza Stark Marked gene: MEGF8 as ready
Intellectual disability syndromic and non-syndromic v0.1255 METTL23 Zornitza Stark Marked gene: METTL23 as ready
Intellectual disability syndromic and non-syndromic v0.1255 MIR17HG Zornitza Stark Marked gene: MIR17HG as ready
Intellectual disability syndromic and non-syndromic v0.1255 WASF1 Zornitza Stark Marked gene: WASF1 as ready
Intellectual disability syndromic and non-syndromic v0.1255 ZNF462 Zornitza Stark Marked gene: ZNF462 as ready
Intellectual disability syndromic and non-syndromic v0.1255 RNF135 Zornitza Stark Marked gene: RNF135 as ready
Intellectual disability syndromic and non-syndromic v0.1255 TTI1 Zornitza Stark Marked gene: TTI1 as ready
Intellectual disability syndromic and non-syndromic v0.1255 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from intellectual disability; seizures; cerebellar atrophy to Intellectual disability
Intellectual disability syndromic and non-syndromic v0.1253 TTI1 Zornitza Stark gene: TTI1 was added
gene: TTI1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: TTI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTI1 were set to 26539891; 30315573
Phenotypes for gene: TTI1 were set to intellectual disability; seizures; cerebellar atrophy
Review for gene: TTI1 was set to AMBER
Added comment: Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1252 SLC25A4 Chirag Patel reviewed gene: SLC25A4: Rating: ; Mode of pathogenicity: None; Publications: PMID: 30013777, 27693233; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, OMIM #617184, Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, OMIM #615418, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, OMIM #609283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1252 SLC25A4 Zornitza Stark Marked gene: SLC25A4 as ready
Intellectual disability syndromic and non-syndromic v0.1252 SLC25A4 Zornitza Stark Phenotypes for gene: SLC25A4 were changed from to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283
Intellectual disability syndromic and non-syndromic v0.1249 SLC25A4 Zornitza Stark reviewed gene: SLC25A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184, Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1246 SLC2A10 Chirag Patel Source Genetic Health Queensland was removed from SLC2A10.
Source Expert list was added to SLC2A10.
Mode of inheritance for gene SLC2A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC2A10 were changed from to Arterial tortuosity syndrome; OMIM #208050
Intellectual disability syndromic and non-syndromic v0.1245 SLC2A10 Chirag Patel reviewed gene: SLC2A10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial tortuosity syndrome, OMIM #208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1244 SLC35A3 Chirag Patel Source Genetic Health Queensland was removed from SLC35A3.
Source Expert list was added to SLC35A3.
Mode of inheritance for gene SLC35A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC35A3 were changed from to ?Arthrogryposis, mental retardation, and seizures; OMIM #615553
Publications for gene SLC35A3 were changed from PMID: 28328131; 24031089 to PMID: 28328131; 24031089
Intellectual disability syndromic and non-syndromic v0.1243 SLC35A3 Chirag Patel reviewed gene: SLC35A3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28328131, 24031089; Phenotypes: ?Arthrogryposis, mental retardation, and seizures, OMIM #615553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1241 SLC25A20 Zornitza Stark Marked gene: SLC25A20 as ready
Intellectual disability syndromic and non-syndromic v0.1241 SLC25A20 Zornitza Stark Phenotypes for gene: SLC25A20 were changed from to Carnitine-acylcarnitine translocase deficiency, MIM#212138
Intellectual disability syndromic and non-syndromic v0.1237 SLC25A20 Zornitza Stark reviewed gene: SLC25A20: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Carnitine-acylcarnitine translocase deficiency, MIM#212138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1233 SLC25A19 Zornitza Stark Marked gene: SLC25A19 as ready
Intellectual disability syndromic and non-syndromic v0.1233 SMCHD1 Chirag Patel Source Genetic Health Queensland was removed from SMCHD1.
Source Expert list was added to SMCHD1.
Mode of inheritance for gene SMCHD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMCHD1 were changed from to Bosma arhinia microphthalmia syndrome, OMIM #603457; Fascioscapulohumeral muscular dystrophy 2, digenic; OMIM #158901
Intellectual disability syndromic and non-syndromic v0.1231 SMCHD1 Chirag Patel reviewed gene: SMCHD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bosma arhinia microphthalmia syndrome, OMIM #603457, Fascioscapulohumeral muscular dystrophy 2, digenic, OMIM #158901; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1226 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Intellectual disability syndromic and non-syndromic v0.1223 SLC22A5 Zornitza Stark Marked gene: SLC22A5 as ready
Intellectual disability syndromic and non-syndromic v0.1223 SLC22A5 Zornitza Stark Phenotypes for gene: SLC22A5 were changed from to Carnitine deficiency, systemic primary, MIM#212140
Intellectual disability syndromic and non-syndromic v0.1221 SLC22A5 Zornitza Stark reviewed gene: SLC22A5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Carnitine deficiency, systemic primary, MIM#212140; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.1219 SLC20A2 Zornitza Stark Marked gene: SLC20A2 as ready
Intellectual disability syndromic and non-syndromic v0.1214 SLC1A3 Zornitza Stark commented on gene: SLC1A3: ID is not part of the phenotype.
Intellectual disability syndromic and non-syndromic v0.1211 SLC1A3 Zornitza Stark Marked gene: SLC1A3 as ready
Intellectual disability syndromic and non-syndromic v0.1208 SPART Chirag Patel Source Genetic Health Queensland was removed from SPART.
Source Expert list was added to SPART.
Mode of inheritance for gene SPART was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPART were changed from to Troyer syndrome; OMIM #275900
Publications for gene SPART were changed from PMID: 26003402; 28679690; 27112432; 20437587; 12134148; 18413476; 31314595; 28875386 to PMID: 26003402; 28679690; 27112432; 20437587; 12134148; 18413476; 31314595; 28875386
Intellectual disability syndromic and non-syndromic v0.1207 SPART Chirag Patel edited their review of gene: SPART: Changed publications: PMID: 26003402, 28679690, 27112432, 20437587, 12134148, 18413476, 31314595, 28875386
Intellectual disability syndromic and non-syndromic v0.1207 SPART Chirag Patel changed review comment from: > 5 families reported, with ID as part of phenotype.; to: Numerous families reported, with ID as part of phenotype.
Intellectual disability syndromic and non-syndromic v0.1207 SPART Chirag Patel reviewed gene: SPART: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26003402, 28679690, 27112432, 20437587, 12134148, 18413476; Phenotypes: Troyer syndrome, OMIM # 275900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1206 SPEG Chirag Patel Source Genetic Health Queensland was removed from SPEG.
Source Expert list was added to SPEG.
Mode of inheritance for gene SPEG was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPEG were changed from to Centronuclear myopathy 5; OMIM #615959
Intellectual disability syndromic and non-syndromic v0.1205 SPEG Chirag Patel reviewed gene: SPEG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Centronuclear myopathy 5, OMIM #615959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1205 SLC1A1 Zornitza Stark Marked gene: SLC1A1 as ready
Intellectual disability syndromic and non-syndromic v0.1205 SLC1A1 Zornitza Stark Phenotypes for gene: SLC1A1 were changed from to Dicarboxylic aminoaciduria, MIM#222730
Intellectual disability syndromic and non-syndromic v0.1203 SLC1A1 Zornitza Stark reviewed gene: SLC1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dicarboxylic aminoaciduria, MIM#222730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1203 SLC19A2 Zornitza Stark Marked gene: SLC19A2 as ready
Intellectual disability syndromic and non-syndromic v0.1200 SLC12A1 Zornitza Stark Marked gene: SLC12A1 as ready
Intellectual disability syndromic and non-syndromic v0.1200 SLC12A1 Zornitza Stark Phenotypes for gene: SLC12A1 were changed from to Bartter syndrome, type 1, MIM#601678
Intellectual disability syndromic and non-syndromic v0.1197 SLC12A1 Zornitza Stark reviewed gene: SLC12A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 1, MIM#601678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1197 SH3TC2 Zornitza Stark Marked gene: SH3TC2 as ready
Intellectual disability syndromic and non-syndromic v0.1197 SH3TC2 Zornitza Stark Phenotypes for gene: SH3TC2 were changed from to Charcot-Marie-Tooth disease, type 4C, MIM#601596
Intellectual disability syndromic and non-syndromic v0.1194 SH3TC2 Zornitza Stark reviewed gene: SH3TC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4C, MIM#601596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1194 SPG7 Chirag Patel Source Genetic Health Queensland was removed from SPG7.
Source Expert list was added to SPG7.
Mode of inheritance for gene SPG7 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SPG7 were changed from to Spastic paraplegia 7, autosomal recessive; OMIM #607259
Intellectual disability syndromic and non-syndromic v0.1193 SPG7 Chirag Patel reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 7, autosomal recessive, OMIM #607259; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1190 SPTLC1 Chirag Patel Source Genetic Health Queensland was removed from SPTLC1.
Source Expert list was added to SPTLC1.
Mode of inheritance for gene SPTLC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPTLC1 were changed from to Neuropathy, hereditary sensory and autonomic, type IA; OMIM #162400
Intellectual disability syndromic and non-syndromic v0.1189 SPTLC1 Chirag Patel reviewed gene: SPTLC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IA, OMIM #162400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1172 SGCA Zornitza Stark Marked gene: SGCA as ready
Intellectual disability syndromic and non-syndromic v0.1172 SGCA Zornitza Stark Phenotypes for gene: SGCA were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 3, MIM#608099
Intellectual disability syndromic and non-syndromic v0.1170 SGCA Zornitza Stark reviewed gene: SGCA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 3, MIM#608099; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.1170 SFXN4 Zornitza Stark Marked gene: SFXN4 as ready
Intellectual disability syndromic and non-syndromic v0.1167 SF3B4 Zornitza Stark Marked gene: SF3B4 as ready
Intellectual disability syndromic and non-syndromic v0.1164 SEPSECS Zornitza Stark Marked gene: SEPSECS as ready
Intellectual disability syndromic and non-syndromic v0.1164 SEPSECS Zornitza Stark Phenotypes for gene: SEPSECS were changed from to Pontocerebellar hypoplasia type 2D, MIM#613811
Intellectual disability syndromic and non-syndromic v0.1161 SEPSECS Zornitza Stark reviewed gene: SEPSECS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12920088, 25044680; Phenotypes: Pontocerebellar hypoplasia type 2D, MIM#613811; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1161 SEMA3E Zornitza Stark reviewed gene: SEMA3E: Rating: AMBER; Mode of pathogenicity: None; Publications: 15235037, 31691538, 31464029; Phenotypes: CHARGE syndrome, MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1161 SELENON Zornitza Stark Marked gene: SELENON as ready
Intellectual disability syndromic and non-syndromic v0.1161 SELENON Zornitza Stark Phenotypes for gene: SELENON were changed from to Muscular dystrophy, rigid spine, 1, MIM# 602771; Myopathy, congenital, with fiber-type disproportion, MIM# 255310
Intellectual disability syndromic and non-syndromic v0.1158 SELENON Zornitza Stark reviewed gene: SELENON: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, rigid spine, 1, MIM# 602771, Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1158 SELENOI Zornitza Stark Marked gene: SELENOI as ready
Intellectual disability syndromic and non-syndromic v0.1158 SELENOI Zornitza Stark gene: SELENOI was added
gene: SELENOI was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: SELENOI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SELENOI were set to 28052917
Phenotypes for gene: SELENOI were set to developmental delay; spasticity; periventricular white mater abnormalities; peripheral neuropathy; seizures; bifid uvula in some affected individuals; microcephaly
Review for gene: SELENOI was set to RED
Added comment: Single family only, four sibs, supportive biochemical evidence. Borderline amber/red gene, only mild ID described, seems to be more of a progressive neurometabolic condition based on limited evidence.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1153 TBC1D20 Chirag Patel edited their review of gene: TBC1D20: Added comment: Liegel et al. (2013) analyzed the candidate gene TBC1D20 and identified homozygous mutations in 7 patients diagnosed with Warburg Micro syndrome from 5 families of different ethnic origins. Evaluation of human fibroblasts deficient in TBC1D20 function identified aberrant lipid droplet formation.; Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.1153 TBC1D20 Chirag Patel Source Genetic Health Queensland was removed from TBC1D20.
Source Expert list was added to TBC1D20.
Mode of inheritance for gene TBC1D20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBC1D20 were changed from to Warburg micro syndrome 4; OMIM #615663
Publications for gene TBC1D20 were changed from PubMed: 24239381 to PubMed: 24239381
Intellectual disability syndromic and non-syndromic v0.1152 TBC1D20 Chirag Patel reviewed gene: TBC1D20: Rating: RED; Mode of pathogenicity: None; Publications: PubMed: 24239381; Phenotypes: Warburg micro syndrome 4, OMIM #615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1147 SCN1B Zornitza Stark Marked gene: SCN1B as ready
Intellectual disability syndromic and non-syndromic v0.1147 SCN1B Zornitza Stark Phenotypes for gene: SCN1B were changed from to Epileptic encephalopathy, early infantile, 52, MIM#617350
Intellectual disability syndromic and non-syndromic v0.1145 SCN1B Zornitza Stark reviewed gene: SCN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 52, MIM#617350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1145 TDP2 Chirag Patel Source Genetic Health Queensland was removed from TDP2.
Source Expert list was added to TDP2.
Mode of inheritance for gene TDP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TDP2 were changed from to Spinocerebellar ataxia, autosomal recessive 23; OMIM #616949
Publications for gene TDP2 were changed from PMID: 31410782; 30109272; 24658003 to PMID: 31410782; 30109272; 24658003
Intellectual disability syndromic and non-syndromic v0.1144 TDP2 Chirag Patel reviewed gene: TDP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31410782, 30109272, 24658003; Phenotypes: Spinocerebellar ataxia, autosomal recessive 23, OMIM #616949; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1144 TERT Chirag Patel Source Genetic Health Queensland was removed from TERT.
Source Expert list was added to TERT.
Mode of inheritance for gene TERT was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TERT were changed from to Dyskeratosis congenita, autosomal dominant 2, OMIM #613989; Dyskeratosis congenita, autosomal recessive 4, OMIM #613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM #614742
Intellectual disability syndromic and non-syndromic v0.1143 TERT Chirag Patel reviewed gene: TERT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita, autosomal dominant 2, OMIM #613989, Dyskeratosis congenita, autosomal recessive 4, OMIM #613989, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM #614742; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1141 TFAP2A Chirag Patel commented on gene: TFAP2A: no ID as part of phenotype.
Intellectual disability syndromic and non-syndromic v0.1140 TFAP2B Chirag Patel Source Genetic Health Queensland was removed from TFAP2B.
Source Expert list was added to TFAP2B.
Mode of inheritance for gene TFAP2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TFAP2B were changed from to Char syndrome, OMIM #169100; Patent ductus arteriosus 2, OMIM #617035
Intellectual disability syndromic and non-syndromic v0.1139 TFAP2B Chirag Patel reviewed gene: TFAP2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Char syndrome, OMIM #169100, Patent ductus arteriosus 2, OMIM #617035; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1138 TFG Chirag Patel Source Genetic Health Queensland was removed from TFG.
Source Expert list was added to TFG.
Mode of inheritance for gene TFG was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TFG were changed from to ?Spastic paraplegia 57, autosomal recessive, OMIM #615658; Hereditary motor and sensory neuropathy, Okinawa type, OMIM #604484
Intellectual disability syndromic and non-syndromic v0.1137 TFG Chirag Patel reviewed gene: TFG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Spastic paraplegia 57, autosomal recessive, OMIM #615658, Hereditary motor and sensory neuropathy, Okinawa type, OMIM #604484; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1127 TKT Chirag Patel Source Genetic Health Queensland was removed from TKT.
Source Expert list was added to TKT.
Mode of inheritance for gene TKT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TKT were changed from to Short stature, developmental delay, and congenital heart defects; OMIM #617044
Publications for gene TKT were changed from PubMed: 27259054 to PubMed: 27259054
Intellectual disability syndromic and non-syndromic v0.1126 TKT Chirag Patel reviewed gene: TKT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 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 v0.1125 SCN11A Zornitza Stark Marked gene: SCN11A as ready
Intellectual disability syndromic and non-syndromic v0.1125 SCN11A Zornitza Stark Phenotypes for gene: SCN11A were changed from to Neuropathy, hereditary sensory and autonomic, type VII, MIM#615548
Intellectual disability syndromic and non-syndromic v0.1122 SCN11A Zornitza Stark reviewed gene: SCN11A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type VII, MIM#615548; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1122 SBF1 Zornitza Stark Marked gene: SBF1 as ready
Intellectual disability syndromic and non-syndromic v0.1122 SBF1 Zornitza Stark Phenotypes for gene: SBF1 were changed from to Charcot-Marie-Tooth disease, type 4B3, MIM# 615284
Intellectual disability syndromic and non-syndromic v0.1119 SBF1 Zornitza Stark reviewed gene: SBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24799518, 23749797, 30039846, 28902413; Phenotypes: Charcot-Marie-Tooth disease, type 4B3, MIM# 615284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1119 SBDS Zornitza Stark Marked gene: SBDS as ready
Intellectual disability syndromic and non-syndromic v0.1115 SARS2 Zornitza Stark Marked gene: SARS2 as ready
Intellectual disability syndromic and non-syndromic v0.1115 SARS2 Zornitza Stark Gene: sars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.1115 SARS2 Zornitza Stark Phenotypes for gene: SARS2 were changed from to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845
Intellectual disability syndromic and non-syndromic v0.1114 SARS2 Zornitza Stark Publications for gene: SARS2 were set to
Intellectual disability syndromic and non-syndromic v0.1113 SARS2 Zornitza Stark Mode of inheritance for gene: SARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1112 SARS2 Zornitza Stark reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21255763, 24034276; Phenotypes: Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1112 SALL1 Zornitza Stark Marked gene: SALL1 as ready
Intellectual disability syndromic and non-syndromic v0.1109 RUBCN Zornitza Stark Marked gene: RUBCN as ready
Intellectual disability syndromic and non-syndromic v0.1109 RUBCN Zornitza Stark Phenotypes for gene: RUBCN were changed from to Spinocerebellar ataxia, autosomal recessive 15, MIM#615705
Intellectual disability syndromic and non-syndromic v0.1106 RUBCN Zornitza Stark reviewed gene: RUBCN: Rating: RED; Mode of pathogenicity: None; Publications: 30237576, 20826435, 23728897; Phenotypes: Spinocerebellar ataxia, autosomal recessive 15, MIM#615705; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.1106 RTN4IP1 Zornitza Stark Phenotypes for gene: RTN4IP1 were changed from to Optic atrophy 10 with or without ataxia, mental retardation, and seizures, MIM#616732
Intellectual disability syndromic and non-syndromic v0.1103 RTN4IP1 Zornitza Stark reviewed gene: RTN4IP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26593267; Phenotypes: Optic atrophy 10 with or without ataxia, mental retardation, and seizures, MIM#616732; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1103 RPS28 Zornitza Stark Marked gene: RPS28 as ready
Intellectual disability syndromic and non-syndromic v0.1100 RPS19 Zornitza Stark Marked gene: RPS19 as ready
Intellectual disability syndromic and non-syndromic v0.1097 RPL11 Zornitza Stark Marked gene: RPL11 as ready
Intellectual disability syndromic and non-syndromic v0.1094 RORA Zornitza Stark Marked gene: RORA as ready
Intellectual disability syndromic and non-syndromic v0.1093 RORA Zornitza Stark gene: RORA was added
gene: RORA was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: RORA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RORA were set to 29656859
Phenotypes for gene: RORA were set to Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM#618060
Mode of pathogenicity for gene: RORA was set to Other
Review for gene: RORA was set to GREEN
Added comment: Eleven unrelated individuals with de novo variants in this gene; postulated that some variants exert dominant-negative effect resulting in a more severe phenotype than the LoF variants.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1092 RNU4ATAC Zornitza Stark Marked gene: RNU4ATAC as ready
Intellectual disability syndromic and non-syndromic v0.1092 RNU4ATAC Zornitza Stark Phenotypes for gene: RNU4ATAC were changed from to Microcephalic osteodysplastic primordial dwarfism, type I, MIM#210710; Roifman syndrome, MIM#616651
Intellectual disability syndromic and non-syndromic v0.1090 RNU4ATAC Zornitza Stark reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: Microcephalic osteodysplastic primordial dwarfism, type I, MIM#210710, Roifman syndrome, MIM#616651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1090 RMRP Zornitza Stark Marked gene: RMRP as ready
Intellectual disability syndromic and non-syndromic v0.1087 RIN2 Zornitza Stark Marked gene: RIN2 as ready
Intellectual disability syndromic and non-syndromic v0.1084 RHOBTB2 Zornitza Stark Marked gene: RHOBTB2 as ready
Intellectual disability syndromic and non-syndromic v0.1083 RHOBTB2 Zornitza Stark gene: RHOBTB2 was added
gene: RHOBTB2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: RHOBTB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RHOBTB2 were set to 29768694; 29276004
Phenotypes for gene: RHOBTB2 were set to Epileptic encephalopathy, early infantile, 64, MIM#618004
Review for gene: RHOBTB2 was set to GREEN
Added comment: 13 individuals from unrelated families reported in the literature in 2018 with de novo variants in this gene and ID/EE.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1082 RFX6 Zornitza Stark Marked gene: RFX6 as ready
Intellectual disability syndromic and non-syndromic v0.1079 RET Zornitza Stark Marked gene: RET as ready
Intellectual disability syndromic and non-syndromic v0.1079 RET Zornitza Stark Phenotypes for gene: RET were changed from to Central hypoventilation syndrome, congenital, MIM#209880; Medullary thyroid carcinoma, MIM#155240; Multiple endocrine neoplasia IIA, MIM#171400; Multiple endocrine neoplasia IIB, MIM#162300
Intellectual disability syndromic and non-syndromic v0.1076 RET Zornitza Stark reviewed gene: RET: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Central hypoventilation syndrome, congenital, MIM#209880, Medullary thyroid carcinoma, MIM#155240, Multiple endocrine neoplasia IIA, MIM#171400, Multiple endocrine neoplasia IIB, MIM#162300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1076 RECQL4 Zornitza Stark Marked gene: RECQL4 as ready
Intellectual disability syndromic and non-syndromic v0.1073 RBPJ Zornitza Stark Marked gene: RBPJ as ready
Intellectual disability syndromic and non-syndromic v0.1070 RBM8A Zornitza Stark Marked gene: RBM8A as ready
Intellectual disability syndromic and non-syndromic v0.1065 TP63 Chirag Patel Source Genetic Health Queensland was removed from TP63.
Source Expert list was added to TP63.
Mode of inheritance for gene TP63 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP63 were changed from to ADULT syndrome, OMIM #103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292; Hay-Wells syndrome, OMIM #106260; Limb-mammary syndrome, OMIM #603543; Orofacial cleft 8, OMIM #618149; Rapp-Hodgkin syndrome, OMIM #129400; Split-hand/foot malformation 4, OMIM #605289
Intellectual disability syndromic and non-syndromic v0.1063 TP63 Chirag Patel reviewed gene: TP63: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ADULT syndrome, OMIM #103285, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292, Hay-Wells syndrome, OMIM #106260, Limb-mammary syndrome, OMIM #603543, Orofacial cleft 8, OMIM #618149, Rapp-Hodgkin syndrome, OMIM #129400, Split-hand/foot malformation 4, OMIM #605289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1063 TPP1 Chirag Patel Source Genetic Health Queensland was removed from TPP1.
Source Expert list was added to TPP1.
Mode of inheritance for gene TPP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPP1 were changed from to Ceroid lipofuscinosis, neuronal, 2, OMIM #204500; Spinocerebellar ataxia, autosomal recessive 7, OMIM #609270
Intellectual disability syndromic and non-syndromic v0.1062 TPP1 Chirag Patel reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 2, OMIM #204500, Spinocerebellar ataxia, autosomal recessive 7, OMIM #609270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1061 TRAF7 Chirag Patel reviewed gene: TRAF7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29961569; Phenotypes: Cardiac, facial, and digital anomalies with developmental delay, OMIM #618164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1061 TRAF7 Chirag Patel gene: TRAF7 was added
gene: TRAF7 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRAF7 were set to PMID: 29961569
Phenotypes for gene: TRAF7 were set to Cardiac, facial, and digital anomalies with developmental delay; OMIM #618164
Intellectual disability syndromic and non-syndromic v0.1060 TRAPPC11 Chirag Patel Source Genetic Health Queensland was removed from TRAPPC11.
Source Expert list was added to TRAPPC11.
Mode of inheritance for gene TRAPPC11 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAPPC11 were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 18; OMIM #615356
Publications for gene TRAPPC11 were changed from PMID: 23830518; 27707803 to PMID: 23830518; 27707803
Intellectual disability syndromic and non-syndromic v0.1059 TRAPPC11 Chirag Patel reviewed gene: TRAPPC11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23830518, 27707803; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18, OMIM #615356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1058 RBM28 Zornitza Stark Marked gene: RBM28 as ready
Intellectual disability syndromic and non-syndromic v0.1054 RAPSN Zornitza Stark Marked gene: RAPSN as ready
Intellectual disability syndromic and non-syndromic v0.1051 RANBP2 Zornitza Stark Marked gene: RANBP2 as ready
Intellectual disability syndromic and non-syndromic v0.1048 RAC3 Zornitza Stark Marked gene: RAC3 as ready
Intellectual disability syndromic and non-syndromic v0.1045 RAB40AL Zornitza Stark Marked gene: RAB40AL as ready
Intellectual disability syndromic and non-syndromic v0.1045 RAB40AL Zornitza Stark Phenotypes for gene: RAB40AL were changed from to MENTAL RETARDATION, X-LINKED, SYNDROMIC, MARTIN-PROBST TYPE
Intellectual disability syndromic and non-syndromic v0.1041 RAB40AL Zornitza Stark reviewed gene: RAB40AL: Rating: RED; Mode of pathogenicity: None; Publications: 25044830; Phenotypes: MENTAL RETARDATION, X-LINKED, SYNDROMIC, MARTIN-PROBST TYPE; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.1041 RAB27A Zornitza Stark Marked gene: RAB27A as ready
Intellectual disability syndromic and non-syndromic v0.1038 PYGL Zornitza Stark Marked gene: PYGL as ready
Intellectual disability syndromic and non-syndromic v0.1035 PUM1 Zornitza Stark Marked gene: PUM1 as ready
Intellectual disability syndromic and non-syndromic v0.1035 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from to Spinocerebellar ataxia 47, MIM#617931
Intellectual disability syndromic and non-syndromic v0.1031 PUM1 Zornitza Stark reviewed gene: PUM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29474920, 25768905; Phenotypes: Spinocerebellar ataxia 47, MIM#617931; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1031 PSAP Zornitza Stark Marked gene: PSAP as ready
Intellectual disability syndromic and non-syndromic v0.1029 PRX Zornitza Stark Marked gene: PRX as ready
Intellectual disability syndromic and non-syndromic v0.1029 PRX Zornitza Stark Phenotypes for gene: PRX were changed from to Charcot-Marie-Tooth disease, type 4F, MIM#614895
Intellectual disability syndromic and non-syndromic v0.1026 PRX Zornitza Stark reviewed gene: PRX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4F, MIM#614895; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1026 PRRX1 Zornitza Stark Marked gene: PRRX1 as ready
Intellectual disability syndromic and non-syndromic v0.1024 PRR12 Zornitza Stark Marked gene: PRR12 as ready
Intellectual disability syndromic and non-syndromic v0.1022 PRR12 Zornitza Stark gene: PRR12 was added
gene: PRR12 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PRR12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRR12 were set to 29556724
Review for gene: PRR12 was set to GREEN
Added comment: Three unrelated individuals reported with de novo LoF variants; in addition, another individual with translocation disrupting gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.1021 PRKRA Zornitza Stark Marked gene: PRKRA as ready
Intellectual disability syndromic and non-syndromic v0.1018 PRKN Zornitza Stark Marked gene: PRKN as ready
Intellectual disability syndromic and non-syndromic v0.1018 PRKN Zornitza Stark Phenotypes for gene: PRKN were changed from to Parkinson disease, juvenile, type 2, MIM#600116
Intellectual disability syndromic and non-syndromic v0.1015 PRKN Zornitza Stark reviewed gene: PRKN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease, juvenile, type 2, MIM#600116; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1015 PRKDC Zornitza Stark Marked gene: PRKDC as ready
Intellectual disability syndromic and non-syndromic v0.1011 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from to Acrodysostosis 1, with or without hormone resistance, MIM#101800
Intellectual disability syndromic and non-syndromic v0.1010 PRKAR1A Zornitza Stark Mode of inheritance for gene: PRKAR1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1009 PRKAR1A Zornitza Stark reviewed gene: PRKAR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM#101800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1009 PRICKLE1 Zornitza Stark Marked gene: PRICKLE1 as ready
Intellectual disability syndromic and non-syndromic v0.1007 PRF1 Zornitza Stark Marked gene: PRF1 as ready
Intellectual disability syndromic and non-syndromic v0.1004 PREPL Zornitza Stark Marked gene: PREPL as ready
Intellectual disability syndromic and non-syndromic v0.1000 PRDM8 Zornitza Stark Marked gene: PRDM8 as ready
Intellectual disability syndromic and non-syndromic v0.996 PPP1R21 Zornitza Stark Marked gene: PPP1R21 as ready
Intellectual disability syndromic and non-syndromic v0.995 PPP1R21 Zornitza Stark gene: PPP1R21 was added
gene: PPP1R21 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: PPP1R21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP1R21 were set to 30520571
Phenotypes for gene: PPP1R21 were set to Hypotonia; intellectual disability; white matter abnormalities
Review for gene: PPP1R21 was set to GREEN
Added comment: At least four unrelated families reported with bi-allelic variants in this gene.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.994 PPOX Zornitza Stark Marked gene: PPOX as ready
Intellectual disability syndromic and non-syndromic v0.994 PPOX Zornitza Stark Phenotypes for gene: PPOX were changed from to Porphyria variegata, MIM#176200
Intellectual disability syndromic and non-syndromic v0.991 PPOX Zornitza Stark reviewed gene: PPOX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Porphyria variegata, MIM#176200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.991 PPM1K Zornitza Stark Marked gene: PPM1K as ready
Intellectual disability syndromic and non-syndromic v0.991 PPM1K Zornitza Stark Phenotypes for gene: PPM1K were changed from to Maple syrup urine disease, mild variant, MIM#615135
Intellectual disability syndromic and non-syndromic v0.987 PPM1K Zornitza Stark reviewed gene: PPM1K: Rating: RED; Mode of pathogenicity: None; Publications: 23086801; Phenotypes: Maple syrup urine disease, mild variant, MIM#615135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.987 POP1 Zornitza Stark Marked gene: POP1 as ready
Intellectual disability syndromic and non-syndromic v0.984 PON3 Zornitza Stark Marked gene: PON3 as ready
Intellectual disability syndromic and non-syndromic v0.983 POMK Zornitza Stark commented on gene: POMK: ID is part of the phenotype.
Intellectual disability syndromic and non-syndromic v0.983 POMK Zornitza Stark Marked gene: POMK as ready
Intellectual disability syndromic and non-syndromic v0.983 POMK Zornitza Stark Phenotypes for gene: POMK were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, MIM#615249
Intellectual disability syndromic and non-syndromic v0.981 POMK Zornitza Stark reviewed gene: POMK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, MIM#615249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.981 POC1A Zornitza Stark Marked gene: POC1A as ready
Intellectual disability syndromic and non-syndromic v0.978 PNPT1 Zornitza Stark Marked gene: PNPT1 as ready
Intellectual disability syndromic and non-syndromic v0.976 PNP Zornitza Stark Marked gene: PNP as ready
Intellectual disability syndromic and non-syndromic v0.973 PLOD3 Zornitza Stark Marked gene: PLOD3 as ready
Intellectual disability syndromic and non-syndromic v0.973 PLOD3 Zornitza Stark Added comment: Comment when marking as ready: Two other reports identified, one of connective tissue/EB phenotype and the other in a large study reporting multiple emerging genes in consanguineous families
Intellectual disability syndromic and non-syndromic v0.969 PIP5K1B Zornitza Stark Marked gene: PIP5K1B as ready
Intellectual disability syndromic and non-syndromic v0.968 PINK1 Zornitza Stark Marked gene: PINK1 as ready
Intellectual disability syndromic and non-syndromic v0.968 PINK1 Zornitza Stark Phenotypes for gene: PINK1 were changed from to Parkinson disease 6, early onset, MIM#605909
Intellectual disability syndromic and non-syndromic v0.965 PINK1 Zornitza Stark reviewed gene: PINK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease 6, early onset, MIM#605909; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.965 PIK3R1 Zornitza Stark Marked gene: PIK3R1 as ready
Intellectual disability syndromic and non-syndromic v0.960 PHKG2 Zornitza Stark Marked gene: PHKG2 as ready
Intellectual disability syndromic and non-syndromic v0.957 PHKA2 Zornitza Stark Marked gene: PHKA2 as ready
Intellectual disability syndromic and non-syndromic v0.954 PHIP Zornitza Stark Marked gene: PHIP as ready
Intellectual disability syndromic and non-syndromic v0.953 PHIP Zornitza Stark gene: PHIP was added
gene: PHIP was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert list
Mode of inheritance for gene: PHIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHIP were set to 29209020; 27900362; 23033978
Phenotypes for gene: PHIP were set to Chung-Jansen syndrome, MIM#617991
Review for gene: PHIP was set to GREEN
Added comment: Recent large case series describing 20 individuals; variable expressivity, some inherited from mildly affected parents, most de novo.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.952 PHC1 Zornitza Stark Marked gene: PHC1 as ready
Intellectual disability syndromic and non-syndromic v0.952 PHC1 Zornitza Stark Phenotypes for gene: PHC1 were changed from to Microcephaly 11, primary, autosomal recessive, MIM#615414
Intellectual disability syndromic and non-syndromic v0.948 PHC1 Zornitza Stark reviewed gene: PHC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23418308; Phenotypes: Microcephaly 11, primary, autosomal recessive, MIM#615414; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.948 PDP1 Zornitza Stark Marked gene: PDP1 as ready
Intellectual disability syndromic and non-syndromic v0.945 PDHB Zornitza Stark Marked gene: PDHB as ready
Intellectual disability syndromic and non-syndromic v0.943 PDGFB Zornitza Stark Marked gene: PDGFB as ready
Intellectual disability syndromic and non-syndromic v0.940 PDE6D Zornitza Stark Marked gene: PDE6D as ready
Intellectual disability syndromic and non-syndromic v0.937 PDE11A Zornitza Stark Marked gene: PDE11A as ready
Intellectual disability syndromic and non-syndromic v0.937 PDE11A Zornitza Stark Phenotypes for gene: PDE11A were changed from to Pigmented nodular adrenocortical disease, primary, 2, MIM#610475
Intellectual disability syndromic and non-syndromic v0.934 PDE11A Zornitza Stark reviewed gene: PDE11A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pigmented nodular adrenocortical disease, primary, 2, MIM#610475; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.934 OXR1 Zornitza Stark Marked gene: OXR1 as ready
Intellectual disability syndromic and non-syndromic v0.933 OXR1 Zornitza Stark gene: OXR1 was added
gene: OXR1 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: OXR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXR1 were set to 31785787
Phenotypes for gene: OXR1 were set to Intellectual disability; seizures; cerebellar atrophy
Review for gene: OXR1 was set to GREEN
Added comment: Five individuals from three families.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.932 TMX2 Zornitza Stark Marked gene: TMX2 as ready
Intellectual disability syndromic and non-syndromic v0.931 TMX2 Zornitza Stark gene: TMX2 was added
gene: TMX2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Literature
Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMX2 were set to 31735293; 31586943
Phenotypes for gene: TMX2 were set to Microcephaly; ID; brain malformations
Review for gene: TMX2 was set to GREEN
Added comment: 14 individuals from 10 unrelated families with bi-allelic variants in this gene (31735293) and another four families with recurrent variant (31586943).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.930 PDE10A Zornitza Stark Marked gene: PDE10A as ready
Intellectual disability syndromic and non-syndromic v0.930 PDE10A Zornitza Stark Added comment: Comment when marking as ready: Note that allelic disorder, Striatal degeneration, autosomal dominant, MIM#616922, is caused by heterozygous variants and ID is not part of the phenotype.
Intellectual disability syndromic and non-syndromic v0.927 PCYT2 Zornitza Stark Marked gene: PCYT2 as ready
Intellectual disability syndromic and non-syndromic v0.926 PCYT2 Zornitza Stark gene: PCYT2 was added
gene: PCYT2 was added to Intellectual disability, syndromic and non-syndromic_GHQ_VCGS. Sources: Expert Review
Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCYT2 were set to 31637422
Phenotypes for gene: PCYT2 were set to Global developmental delay with regression; spastic para- or tetra paresis; epilepsy; progressive cerebral and cerebellar atrophy
Review for gene: PCYT2 was set to GREEN
Added comment: Five unrelated individuals. Variants are hypomorphic.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.925 PCLO Zornitza Stark Marked gene: PCLO as ready
Intellectual disability syndromic and non-syndromic v0.924 PCLO Zornitza Stark Phenotypes for gene: PCLO were changed from to Pontocerebellar hypoplasia, type 3, MIM#608027
Intellectual disability syndromic and non-syndromic v0.920 PCDH9 Zornitza Stark Marked gene: PCDH9 as ready
Intellectual disability syndromic and non-syndromic v0.919 PCDH15 Zornitza Stark Marked gene: PCDH15 as ready
Intellectual disability syndromic and non-syndromic v0.916 PCDH12 Zornitza Stark Marked gene: PCDH12 as ready
Intellectual disability syndromic and non-syndromic v0.910 PAX3 Zornitza Stark Marked gene: PAX3 as ready
Intellectual disability syndromic and non-syndromic v0.910 PAX3 Zornitza Stark Phenotypes for gene: PAX3 were changed from to Craniofacial-deafness-hand syndrome, MIM#122880; Waardenburg syndrome, type 1, MIM#193500; Waardenburg syndrome, type 3, MIM#148820
Intellectual disability syndromic and non-syndromic v0.907 PAX3 Zornitza Stark reviewed gene: PAX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniofacial-deafness-hand syndrome, MIM#122880, Waardenburg syndrome, type 1, MIM#193500, Waardenburg syndrome, type 3, MIM#148820; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.907 PAX2 Zornitza Stark Marked gene: PAX2 as ready
Intellectual disability syndromic and non-syndromic v0.904 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Intellectual disability syndromic and non-syndromic v0.901 PAM16 Zornitza Stark Marked gene: PAM16 as ready
Intellectual disability syndromic and non-syndromic v0.901 PAM16 Zornitza Stark Phenotypes for gene: PAM16 were changed from to Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, MIM#613320
Intellectual disability syndromic and non-syndromic v0.898 PAM16 Zornitza Stark reviewed gene: PAM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 24786642, 27354339; Phenotypes: Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, MIM#613320; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.898 PACS2 Zornitza Stark Marked gene: PACS2 as ready
Intellectual disability syndromic and non-syndromic v0.898 PACS2 Zornitza Stark Phenotypes for gene: PACS2 were changed from to Epileptic encephalopathy, early infantile, 66, MIM#618067
Intellectual disability syndromic and non-syndromic v0.895 PACS2 Zornitza Stark reviewed gene: PACS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29656858; Phenotypes: Epileptic encephalopathy, early infantile, 66, MIM#618067; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.893 NUP62 Zornitza Stark Marked gene: NUP62 as ready
Intellectual disability syndromic and non-syndromic v0.893 NUP62 Zornitza Stark Added comment: Comment when marking as ready: Multiple affected individuals, age of onset variable, may be after viral trigger.
Intellectual disability syndromic and non-syndromic v0.889 NRXN2 Zornitza Stark Marked gene: NRXN2 as ready
Intellectual disability syndromic and non-syndromic v0.885 NR4A2 Zornitza Stark Marked gene: NR4A2 as ready
Intellectual disability syndromic and non-syndromic v0.881 NIN Zornitza Stark Marked gene: NIN as ready
Intellectual disability syndromic and non-syndromic v0.877 NOTCH3 Zornitza Stark Marked gene: NOTCH3 as ready
Intellectual disability syndromic and non-syndromic v0.877 NOTCH3 Zornitza Stark Phenotypes for gene: NOTCH3 were changed from to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310
Intellectual disability syndromic and non-syndromic v0.874 NOTCH3 Zornitza Stark reviewed gene: NOTCH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.874 NOP10 Zornitza Stark Marked gene: NOP10 as ready
Intellectual disability syndromic and non-syndromic v0.870 NHLRC1 Zornitza Stark Marked gene: NHLRC1 as ready
Intellectual disability syndromic and non-syndromic v0.867 NFIB Zornitza Stark Marked gene: NFIB as ready
Intellectual disability syndromic and non-syndromic v0.865 NEGR1 Zornitza Stark Marked gene: NEGR1 as ready
Intellectual disability syndromic and non-syndromic v0.864 NEDD4L Zornitza Stark Marked gene: NEDD4L as ready
Intellectual disability syndromic and non-syndromic v0.864 NEDD4L Zornitza Stark Phenotypes for gene: NEDD4L were changed from to Periventricular nodular heterotopia 7, MIM#617201
Intellectual disability syndromic and non-syndromic v0.862 NEDD4L Zornitza Stark reviewed gene: NEDD4L: Rating: GREEN; Mode of pathogenicity: None; Publications: 27694961; Phenotypes: Periventricular nodular heterotopia 7, MIM#617201; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.862 NECAP1 Zornitza Stark Marked gene: NECAP1 as ready
Intellectual disability syndromic and non-syndromic v0.862 NECAP1 Zornitza Stark Phenotypes for gene: NECAP1 were changed from to Epileptic encephalopathy, early infantile, 21, MIM#615833
Intellectual disability syndromic and non-syndromic v0.859 NECAP1 Zornitza Stark Added comment: Comment on list classification: Three families, but two of these have the same founder variant; no functional data.
Intellectual disability syndromic and non-syndromic v0.858 NECAP1 Zornitza Stark reviewed gene: NECAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24399846, 30626896, 30525121; Phenotypes: Epileptic encephalopathy, early infantile, 21, MIM#615833; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.858 NDUFV2 Zornitza Stark Marked gene: NDUFV2 as ready
Intellectual disability syndromic and non-syndromic v0.858 NDUFV2 Zornitza Stark Phenotypes for gene: NDUFV2 were changed from to Mitochondrial complex I deficiency, nuclear type 7, MIM#618229
Intellectual disability syndromic and non-syndromic v0.855 NDUFV2 Zornitza Stark reviewed gene: NDUFV2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12754703, 26008862, 29554876; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7, MIM#618229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.855 NDUFS6 Zornitza Stark Marked gene: NDUFS6 as ready
Intellectual disability syndromic and non-syndromic v0.855 NDUFS6 Zornitza Stark Phenotypes for gene: NDUFS6 were changed from to Mitochondrial complex I deficiency, nuclear type 9, MIM#618232
Intellectual disability syndromic and non-syndromic v0.852 NDUFS6 Zornitza Stark reviewed gene: NDUFS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15372108, 19259137, 30948790, 22474353; Phenotypes: Mitochondrial complex I deficiency, nuclear type 9, MIM#618232; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.852 NDUFS3 Zornitza Stark Marked gene: NDUFS3 as ready
Intellectual disability syndromic and non-syndromic v0.852 NDUFS3 Zornitza Stark Phenotypes for gene: NDUFS3 were changed from to Mitochondrial complex I deficiency, nuclear type 8, MIM#618230
Intellectual disability syndromic and non-syndromic v0.849 NDUFS3 Zornitza Stark reviewed gene: NDUFS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 14729820, 22499348, 30140060; Phenotypes: Mitochondrial complex I deficiency, nuclear type 8, MIM#618230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.849 NDUFS2 Zornitza Stark Marked gene: NDUFS2 as ready
Intellectual disability syndromic and non-syndromic v0.849 NDUFS2 Zornitza Stark Phenotypes for gene: NDUFS2 were changed from to Mitochondrial complex I deficiency, nuclear type 6, MIM#618228
Intellectual disability syndromic and non-syndromic v0.846 NDUFS2 Zornitza Stark reviewed gene: NDUFS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11220739, 31411514, 29272804; Phenotypes: Mitochondrial complex I deficiency, nuclear type 6, MIM#618228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.846 NDUFB9 Zornitza Stark Phenotypes for gene: NDUFB9 were changed from to Mitochondrial complex I deficiency, nuclear type 24, MIM#618245
Intellectual disability syndromic and non-syndromic v0.843 NDUFB9 Zornitza Stark reviewed gene: NDUFB9: Rating: AMBER; Mode of pathogenicity: None; Publications: 22200994; Phenotypes: Mitochondrial complex I deficiency, nuclear type 24, MIM#618245; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.843 NDUFB3 Zornitza Stark Marked gene: NDUFB3 as ready
Intellectual disability syndromic and non-syndromic v0.843 NDUFB3 Zornitza Stark Phenotypes for gene: NDUFB3 were changed from to Mitochondrial complex I deficiency, nuclear type 25, MIM#618246
Intellectual disability syndromic and non-syndromic v0.840 NDUFB3 Zornitza Stark reviewed gene: NDUFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22277967, 22499348, 27091925; Phenotypes: Mitochondrial complex I deficiency, nuclear type 25, MIM#618246; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.840 NDUFAF6 Zornitza Stark Marked gene: NDUFAF6 as ready
Intellectual disability syndromic and non-syndromic v0.840 NDUFAF6 Zornitza Stark Phenotypes for gene: NDUFAF6 were changed from to Mitochondrial complex I deficiency, nuclear type 17, MIM#618239
Intellectual disability syndromic and non-syndromic v0.837 NDUFAF6 Zornitza Stark reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 18614015; Phenotypes: Mitochondrial complex I deficiency, nuclear type 17, MIM#618239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.837 NDUFAF4 Zornitza Stark Marked gene: NDUFAF4 as ready
Intellectual disability syndromic and non-syndromic v0.837 NDUFAF4 Zornitza Stark Phenotypes for gene: NDUFAF4 were changed from to Mitochondrial complex I deficiency, nuclear type 15, MIM#618237
Intellectual disability syndromic and non-syndromic v0.834 NDUFAF4 Zornitza Stark reviewed gene: NDUFAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 18179882, 28853723; Phenotypes: Mitochondrial complex I deficiency, nuclear type 15, MIM#618237; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.834 NDUFAF3 Zornitza Stark Marked gene: NDUFAF3 as ready
Intellectual disability syndromic and non-syndromic v0.834 NDUFAF3 Zornitza Stark Phenotypes for gene: NDUFAF3 were changed from to Mitochondrial complex I deficiency, nuclear type 18, MIM#618240
Intellectual disability syndromic and non-syndromic v0.831 NDUFAF3 Zornitza Stark reviewed gene: NDUFAF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19463981; Phenotypes: Mitochondrial complex I deficiency, nuclear type 18, MIM#618240; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.831 NDUFAF2 Zornitza Stark Marked gene: NDUFAF2 as ready
Intellectual disability syndromic and non-syndromic v0.831 NDUFAF2 Zornitza Stark Phenotypes for gene: NDUFAF2 were changed from to Mitochondrial complex I deficiency, nuclear type 10, MIM#618233
Intellectual disability syndromic and non-syndromic v0.828 NDUFAF2 Zornitza Stark reviewed gene: NDUFAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 10, MIM#618233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.828 NDUFAF1 Zornitza Stark reviewed gene: NDUFAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17557076, 21931170, 24963768; Phenotypes: Mitochondrial complex I deficiency, nuclear type 11, MIM#618234; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.828 NDUFA9 Zornitza Stark Marked gene: NDUFA9 as ready
Intellectual disability syndromic and non-syndromic v0.828 NDUFA9 Zornitza Stark Phenotypes for gene: NDUFA9 were changed from to Mitochondrial complex I deficiency, nuclear type 26, MIM#618247
Intellectual disability syndromic and non-syndromic v0.825 NDUFA9 Zornitza Stark reviewed gene: NDUFA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28671271, 22114105; Phenotypes: Mitochondrial complex I deficiency, nuclear type 26, MIM#618247; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.825 NDUFA2 Zornitza Stark reviewed gene: NDUFA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18513682, 28857146; Phenotypes: Mitochondrial complex I deficiency, nuclear type 13, MIM#618235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.825 NDUFA11 Zornitza Stark Marked gene: NDUFA11 as ready
Intellectual disability syndromic and non-syndromic v0.825 NDUFA11 Zornitza Stark Phenotypes for gene: NDUFA11 were changed from to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236
Intellectual disability syndromic and non-syndromic v0.821 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: AMBER; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.821 NDUFA10 Zornitza Stark Marked gene: NDUFA10 as ready
Intellectual disability syndromic and non-syndromic v0.821 NDUFA10 Zornitza Stark Phenotypes for gene: NDUFA10 were changed from to Mitochondrial complex I deficiency, nuclear type 22, MIM#618243
Intellectual disability syndromic and non-syndromic v0.818 NDUFA10 Zornitza Stark reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 21150889, 26741492; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22, MIM#618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.818 NDN Zornitza Stark Marked gene: NDN as ready
Intellectual disability syndromic and non-syndromic v0.817 NAGS Zornitza Stark Marked gene: NAGS as ready
Intellectual disability syndromic and non-syndromic v0.814 CLCN2 Zornitza Stark Marked gene: CLCN2 as ready
Intellectual disability syndromic and non-syndromic v0.810 CISD2 Zornitza Stark Marked gene: CISD2 as ready
Intellectual disability syndromic and non-syndromic v0.807 CHST14 Zornitza Stark Marked gene: CHST14 as ready
Intellectual disability syndromic and non-syndromic v0.803 CACNA1E Zornitza Stark Marked gene: CACNA1E as ready
Intellectual disability syndromic and non-syndromic v0.802 ATAD1 Zornitza Stark Marked gene: ATAD1 as ready
Intellectual disability syndromic and non-syndromic v0.801 ASTN1 Zornitza Stark Marked gene: ASTN1 as ready
Intellectual disability syndromic and non-syndromic v0.800 ASH1L Zornitza Stark Marked gene: ASH1L as ready
Intellectual disability syndromic and non-syndromic v0.799 AGO3 Zornitza Stark Marked gene: AGO3 as ready
Intellectual disability syndromic and non-syndromic v0.798 ADRA2B Zornitza Stark Marked gene: ADRA2B as ready
Intellectual disability syndromic and non-syndromic v0.798 ADRA2B Zornitza Stark gene: ADRA2B was added
gene: ADRA2B was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: ADRA2B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ADRA2B were set to 24114805; 21937992
Phenotypes for gene: ADRA2B were set to Cortical myoclonus and epilepsy; Intellectual disability
Review for gene: ADRA2B was set to RED
Added comment: Two families reported but same mutation, ?founder effect. Most affected individuals had normal intellect.
Another paper linking to AR intellectual disability but as part of manuscript reporting multiple novel candidates.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.797 CFHR3 Zornitza Stark Marked gene: CFHR3 as ready
Intellectual disability syndromic and non-syndromic v0.794 CFHR1 Zornitza Stark Marked gene: CFHR1 as ready
Intellectual disability syndromic and non-syndromic v0.791 CFH Zornitza Stark Marked gene: CFH as ready
Intellectual disability syndromic and non-syndromic v0.788 CEP89 Zornitza Stark Marked gene: CEP89 as ready
Intellectual disability syndromic and non-syndromic v0.784 CEP63 Zornitza Stark Marked gene: CEP63 as ready
Intellectual disability syndromic and non-syndromic v0.780 CDT1 Zornitza Stark Marked gene: CDT1 as ready
Intellectual disability syndromic and non-syndromic v0.777 CDK6 Zornitza Stark Marked gene: CDK6 as ready
Intellectual disability syndromic and non-syndromic v0.777 CDK6 Zornitza Stark Phenotypes for gene: CDK6 were changed from to Microcephaly 12, primary, autosomal recessive, MIM#616080
Intellectual disability syndromic and non-syndromic v0.773 CDK16 Zornitza Stark Marked gene: CDK16 as ready
Intellectual disability syndromic and non-syndromic v0.769 CD96 Zornitza Stark Marked gene: CD96 as ready
Intellectual disability syndromic and non-syndromic v0.765 CCDC8 Zornitza Stark Marked gene: CCDC8 as ready
Intellectual disability syndromic and non-syndromic v0.761 CCDC78 Zornitza Stark Marked gene: CCDC78 as ready
Intellectual disability syndromic and non-syndromic v0.761 CCDC78 Zornitza Stark Phenotypes for gene: CCDC78 were changed from to Centronuclear myopathy 4, MIM#614807
Intellectual disability syndromic and non-syndromic v0.757 CACNA1G Zornitza Stark Marked gene: CACNA1G as ready
Intellectual disability syndromic and non-syndromic v0.757 CACNA1G Zornitza Stark Phenotypes for gene: CACNA1G were changed from to Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits, MIM#618087
Intellectual disability syndromic and non-syndromic v0.754 CA8 Zornitza Stark Marked gene: CA8 as ready
Intellectual disability syndromic and non-syndromic v0.754 CA8 Zornitza Stark Phenotypes for gene: CA8 were changed from to Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3, MIM#613227
Intellectual disability syndromic and non-syndromic v0.751 CA2 Zornitza Stark Marked gene: CA2 as ready
Intellectual disability syndromic and non-syndromic v0.751 CA2 Zornitza Stark Phenotypes for gene: CA2 were changed from to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730
Intellectual disability syndromic and non-syndromic v0.749 C3orf58 Zornitza Stark Marked gene: C3orf58 as ready
Intellectual disability syndromic and non-syndromic v0.748 C19orf12 Zornitza Stark Marked gene: C19orf12 as ready
Intellectual disability syndromic and non-syndromic v0.745 BSND Zornitza Stark Marked gene: BSND as ready
Intellectual disability syndromic and non-syndromic v0.745 BSND Zornitza Stark Phenotypes for gene: BSND were changed from to Bartter syndrome, type 4a, MIM#602522
Intellectual disability syndromic and non-syndromic v0.743 BRAT1 Zornitza Stark Marked gene: BRAT1 as ready
Intellectual disability syndromic and non-syndromic v0.743 BRAT1 Zornitza Stark Phenotypes for gene: BRAT1 were changed from to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures, MIM#618056
Intellectual disability syndromic and non-syndromic v0.740 BMPER Zornitza Stark Marked gene: BMPER as ready
Intellectual disability syndromic and non-syndromic v0.738 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Intellectual disability syndromic and non-syndromic v0.738 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from to Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM#615290
Intellectual disability syndromic and non-syndromic v0.735 BDNF Zornitza Stark Marked gene: BDNF as ready
Intellectual disability syndromic and non-syndromic v0.732 BBIP1 Zornitza Stark Marked gene: BBIP1 as ready
Intellectual disability syndromic and non-syndromic v0.732 BBIP1 Zornitza Stark Phenotypes for gene: BBIP1 were changed from to Bardet-Biedl syndrome 18, MIM#615995
Intellectual disability syndromic and non-syndromic v0.728 B9D2 Zornitza Stark Marked gene: B9D2 as ready
Intellectual disability syndromic and non-syndromic v0.725 B9D1 Zornitza Stark Marked gene: B9D1 as ready
Intellectual disability syndromic and non-syndromic v0.722 B4GALT1 Zornitza Stark Marked gene: B4GALT1 as ready
Intellectual disability syndromic and non-syndromic v0.719 B3GAT3 Zornitza Stark Marked gene: B3GAT3 as ready
Intellectual disability syndromic and non-syndromic v0.719 B3GAT3 Zornitza Stark Phenotypes for gene: B3GAT3 were changed from to Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM#245600
Intellectual disability syndromic and non-syndromic v0.716 B3GALT6 Zornitza Stark Marked gene: B3GALT6 as ready
Intellectual disability syndromic and non-syndromic v0.713 AHCY Zornitza Stark Marked gene: AHCY as ready
Intellectual disability syndromic and non-syndromic v0.711 ASNS Zornitza Stark Marked gene: ASNS as ready
Intellectual disability syndromic and non-syndromic v0.711 ASNS Zornitza Stark Phenotypes for gene: ASNS were changed from to Asparagine synthetase deficiency, MIM#615574
Intellectual disability syndromic and non-syndromic v0.710 ASL Zornitza Stark Marked gene: ASL as ready
Intellectual disability syndromic and non-syndromic v0.710 ASL Zornitza Stark Phenotypes for gene: ASL were changed from to Argininosuccinic aciduria, MIM#207900
Intellectual disability syndromic and non-syndromic v0.708 ALX3 Zornitza Stark Marked gene: ALX3 as ready
Intellectual disability syndromic and non-syndromic v0.705 ALX1 Zornitza Stark Marked gene: ALX1 as ready
Intellectual disability syndromic and non-syndromic v0.701 ALG14 Zornitza Stark Marked gene: ALG14 as ready
Intellectual disability syndromic and non-syndromic v0.701 ALG14 Zornitza Stark Phenotypes for gene: ALG14 were changed from to Myasthenic syndrome, congenital, 15, without tubular aggregates, MIM#616227; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.698 ALDOB Zornitza Stark Marked gene: ALDOB as ready
Intellectual disability syndromic and non-syndromic v0.698 ALDOB Zornitza Stark Phenotypes for gene: ALDOB were changed from to Fructose intolerance, hereditary, MIM#229600
Intellectual disability syndromic and non-syndromic v0.696 AGA Zornitza Stark Marked gene: AGA as ready
Intellectual disability syndromic and non-syndromic v0.696 AGA Zornitza Stark Phenotypes for gene: AGA were changed from to Aspartylglucosaminuria, MIM#208400
Intellectual disability syndromic and non-syndromic v0.694 ADD3 Zornitza Stark Marked gene: ADD3 as ready
Intellectual disability syndromic and non-syndromic v0.691 ADAT3 Zornitza Stark Marked gene: ADAT3 as ready
Intellectual disability syndromic and non-syndromic v0.691 ADAT3 Zornitza Stark Phenotypes for gene: ADAT3 were changed from to Mental retardation, autosomal recessive 36, MIM#615286
Intellectual disability syndromic and non-syndromic v0.688 ADAMTS10 Zornitza Stark Marked gene: ADAMTS10 as ready
Intellectual disability syndromic and non-syndromic v0.688 ADAMTS10 Zornitza Stark Phenotypes for gene: ADAMTS10 were changed from to Weill-Marchesani syndrome 1, recessive, MIM#277600
Intellectual disability syndromic and non-syndromic v0.686 ACTL6A Zornitza Stark Marked gene: ACTL6A as ready
Intellectual disability syndromic and non-syndromic v0.683 AVPR2 Zornitza Stark Marked gene: AVPR2 as ready
Intellectual disability syndromic and non-syndromic v0.680 AVPR1A Zornitza Stark Marked gene: AVPR1A as ready
Intellectual disability syndromic and non-syndromic v0.679 AVP Zornitza Stark Marked gene: AVP as ready
Intellectual disability syndromic and non-syndromic v0.676 ATXN10 Zornitza Stark Marked gene: ATXN10 as ready
Intellectual disability syndromic and non-syndromic v0.676 ATXN10 Zornitza Stark Phenotypes for gene: ATXN10 were changed from to Spinocerebellar ataxia 10, MIM#603516
Intellectual disability syndromic and non-syndromic v0.673 ATP8A2 Zornitza Stark Marked gene: ATP8A2 as ready
Intellectual disability syndromic and non-syndromic v0.673 ATP8A2 Zornitza Stark Phenotypes for gene: ATP8A2 were changed from to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4, MIM#615268
Intellectual disability syndromic and non-syndromic v0.670 ATP2B3 Zornitza Stark Marked gene: ATP2B3 as ready
Intellectual disability syndromic and non-syndromic v0.670 ATP2B3 Zornitza Stark Phenotypes for gene: ATP2B3 were changed from to Spinocerebellar ataxia, X-linked 1, MIM#302500
Intellectual disability syndromic and non-syndromic v0.667 ATP2A2 Zornitza Stark Marked gene: ATP2A2 as ready
Intellectual disability syndromic and non-syndromic v0.667 ATP2A2 Zornitza Stark Phenotypes for gene: ATP2A2 were changed from to Darier disease, MIM#124200
Intellectual disability syndromic and non-syndromic v0.664 ATP1A3 Zornitza Stark Marked gene: ATP1A3 as ready
Intellectual disability syndromic and non-syndromic v0.661 ATP10A Zornitza Stark Marked gene: ATP10A as ready
Intellectual disability syndromic and non-syndromic v0.658 ARNT2 Zornitza Stark Marked gene: ARNT2 as ready
Intellectual disability syndromic and non-syndromic v0.658 ARNT2 Zornitza Stark Gene: arnt2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.658 ARNT2 Zornitza Stark Phenotypes for gene: ARNT2 were changed from to Webb-Dattani syndrome 615926
Intellectual disability syndromic and non-syndromic v0.657 ARNT2 Zornitza Stark Publications for gene: ARNT2 were set to
Intellectual disability syndromic and non-syndromic v0.656 ARNT2 Zornitza Stark Mode of inheritance for gene: ARNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.655 ARNT2 Zornitza Stark Classified gene: ARNT2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.655 ARNT2 Zornitza Stark Gene: arnt2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.654 ARHGAP31 Zornitza Stark Marked gene: ARHGAP31 as ready
Intellectual disability syndromic and non-syndromic v0.654 ARHGAP31 Zornitza Stark Gene: arhgap31 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.654 ARHGAP31 Zornitza Stark Phenotypes for gene: ARHGAP31 were changed from to Adams-Oliver syndrome 1, MIM#100300
Intellectual disability syndromic and non-syndromic v0.653 ARHGAP31 Zornitza Stark Mode of inheritance for gene: ARHGAP31 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.652 ARHGAP31 Zornitza Stark Classified gene: ARHGAP31 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.652 ARHGAP31 Zornitza Stark Gene: arhgap31 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.651 APTX Zornitza Stark Marked gene: APTX as ready
Intellectual disability syndromic and non-syndromic v0.651 APTX Zornitza Stark Phenotypes for gene: APTX were changed from to Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, MIM#208920
Intellectual disability syndromic and non-syndromic v0.648 ANKH Zornitza Stark Marked gene: ANKH as ready
Intellectual disability syndromic and non-syndromic v0.645 ALS2 Zornitza Stark Marked gene: ALS2 as ready
Intellectual disability syndromic and non-syndromic v0.645 ALS2 Zornitza Stark Phenotypes for gene: ALS2 were changed from to Spastic paralysis, infantile onset ascending, MIM#607225
Intellectual disability syndromic and non-syndromic v0.642 ALDOA Zornitza Stark Marked gene: ALDOA as ready
Intellectual disability syndromic and non-syndromic v0.639 AKR1C2 Zornitza Stark Marked gene: AKR1C2 as ready
Intellectual disability syndromic and non-syndromic v0.636 AKAP6 Zornitza Stark Marked gene: AKAP6 as ready
Intellectual disability syndromic and non-syndromic v0.632 AGTR2 Zornitza Stark Marked gene: AGTR2 as ready
Intellectual disability syndromic and non-syndromic v0.631 AGT Zornitza Stark Marked gene: AGT as ready
Intellectual disability syndromic and non-syndromic v0.631 AGT Zornitza Stark Phenotypes for gene: AGT were changed from to Renal tubular dysgenesis, MIM#267430
Intellectual disability syndromic and non-syndromic v0.628 AGPS Zornitza Stark Marked gene: AGPS as ready
Intellectual disability syndromic and non-syndromic v0.625 AGK Zornitza Stark Marked gene: AGK as ready
Intellectual disability syndromic and non-syndromic v0.622 AGGF1 Zornitza Stark Marked gene: AGGF1 as ready
Intellectual disability syndromic and non-syndromic v0.621 AFG3L2 Zornitza Stark Marked gene: AFG3L2 as ready
Intellectual disability syndromic and non-syndromic v0.618 CHD1 Zornitza Stark Marked gene: CHD1 as ready
Intellectual disability syndromic and non-syndromic v0.617 ADCY5 Zornitza Stark Marked gene: ADCY5 as ready
Intellectual disability syndromic and non-syndromic v0.614 ADAMTSL2 Zornitza Stark Marked gene: ADAMTSL2 as ready
Intellectual disability syndromic and non-syndromic v0.611 ADA2 Zornitza Stark Marked gene: ADA2 as ready
Intellectual disability syndromic and non-syndromic v0.608 MAP4K4 Zornitza Stark Marked gene: MAP4K4 as ready
Intellectual disability syndromic and non-syndromic v0.607 LZTR1 Zornitza Stark Marked gene: LZTR1 as ready
Intellectual disability syndromic and non-syndromic v0.605 LAMB2 Zornitza Stark Marked gene: LAMB2 as ready
Intellectual disability syndromic and non-syndromic v0.603 LZTFL1 Zornitza Stark Marked gene: LZTFL1 as ready
Intellectual disability syndromic and non-syndromic v0.602 LZTFL1 Zornitza Stark reviewed gene: LZTFL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22510444, 23692385, 27312011; Phenotypes: Bardet-Biedl syndrome 17, MIM#615994; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.602 LYST Zornitza Stark Marked gene: LYST as ready
Intellectual disability syndromic and non-syndromic v0.600 LYRM7 Zornitza Stark Marked gene: LYRM7 as ready
Intellectual disability syndromic and non-syndromic v0.600 LYRM7 Zornitza Stark Phenotypes for gene: LYRM7 were changed from to Mitochondrial complex III deficiency, nuclear type 8, MIM#615838
Intellectual disability syndromic and non-syndromic v0.598 LYRM7 Zornitza Stark reviewed gene: LYRM7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex III deficiency, nuclear type 8, MIM#615838; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.598 LMNB1 Zornitza Stark Marked gene: LMNB1 as ready
Intellectual disability syndromic and non-syndromic v0.595 LMNA Zornitza Stark Marked gene: LMNA as ready
Intellectual disability syndromic and non-syndromic v0.594 LIPT1 Zornitza Stark Marked gene: LIPT1 as ready
Intellectual disability syndromic and non-syndromic v0.590 LINGO1 Zornitza Stark Marked gene: LINGO1 as ready
Intellectual disability syndromic and non-syndromic v0.589 LINGO1 Zornitza Stark gene: LINGO1 was added
gene: LINGO1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: LINGO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LINGO1 were set to 28837161
Phenotypes for gene: LINGO1 were set to Mental retardation, autosomal recessive 64, MIM#618103
Review for gene: LINGO1 was set to GREEN
Added comment: Five individuals from two unrelated families, no functional evidence.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.588 LIAS Zornitza Stark Marked gene: LIAS as ready
Intellectual disability syndromic and non-syndromic v0.585 LGI4 Zornitza Stark Marked gene: LGI4 as ready
Intellectual disability syndromic and non-syndromic v0.585 LGI4 Zornitza Stark Phenotypes for gene: LGI4 were changed from to Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468
Intellectual disability syndromic and non-syndromic v0.582 LGI4 Zornitza Stark reviewed gene: LGI4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.582 LBR Zornitza Stark Marked gene: LBR as ready
Intellectual disability syndromic and non-syndromic v0.579 KYNU Zornitza Stark edited their review of gene: KYNU: Changed phenotypes: Hydroxykynureninuria, MIM#236800, Vertebral, cardiac, renal, and limb defects syndrome 2, MIM#617661
Intellectual disability syndromic and non-syndromic v0.579 KYNU Zornitza Stark Marked gene: KYNU as ready
Intellectual disability syndromic and non-syndromic v0.576 KMT5B Zornitza Stark Marked gene: KMT5B as ready
Intellectual disability syndromic and non-syndromic v0.575 KMT5B Zornitza Stark gene: KMT5B was added
gene: KMT5B was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: KMT5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT5B were set to 25363768; 28191889; 29276005
Phenotypes for gene: KMT5B were set to Mental retardation, autosomal dominant 51, MIM#617788
Review for gene: KMT5B was set to GREEN
Added comment: Multiple affected individuals from unrelated families.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.574 KMT2B Zornitza Stark Marked gene: KMT2B as ready
Intellectual disability syndromic and non-syndromic v0.570 KLF8 Zornitza Stark Marked gene: KLF8 as ready
Intellectual disability syndromic and non-syndromic v0.565 KIRREL3 Zornitza Stark Marked gene: KIRREL3 as ready
Intellectual disability syndromic and non-syndromic v0.561 KIF21A Zornitza Stark Marked gene: KIF21A as ready
Intellectual disability syndromic and non-syndromic v0.561 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from to Fibrosis of extraocular muscles, congenital, 1, MIM#135700
Intellectual disability syndromic and non-syndromic v0.558 KIF21A Zornitza Stark reviewed gene: KIF21A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrosis of extraocular muscles, congenital, 1, MIM#135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.558 KIF16B Zornitza Stark Marked gene: KIF16B as ready
Intellectual disability syndromic and non-syndromic v0.554 KDM6B Zornitza Stark Marked gene: KDM6B as ready
Intellectual disability syndromic and non-syndromic v0.553 KDM6B Zornitza Stark gene: KDM6B was added
gene: KDM6B was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: KDM6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM6B were set to 31124279
Phenotypes for gene: KDM6B were set to Intellectual disability
Review for gene: KDM6B was set to GREEN
Added comment: 12 unrelated individuals with de novo variants in this gene, no functional evidence reported but KDM6B involved in histone methylation.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.552 KCTD13 Zornitza Stark Marked gene: KCTD13 as ready
Intellectual disability syndromic and non-syndromic v0.548 KCNMA1 Zornitza Stark Marked gene: KCNMA1 as ready
Intellectual disability syndromic and non-syndromic v0.548 KCNMA1 Zornitza Stark Phenotypes for gene: KCNMA1 were changed from to Cerebellar atrophy, developmental delay, and seizures, MIM# 617643; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM#609446
Intellectual disability syndromic and non-syndromic v0.545 KCNMA1 Zornitza Stark reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27567911, 29545233, 26195193, 31427379; Phenotypes: Cerebellar atrophy, developmental delay, and seizures, MIM# 617643, Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM#609446; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.545 KCNJ1 Zornitza Stark Marked gene: KCNJ1 as ready
Intellectual disability syndromic and non-syndromic v0.545 KCNJ1 Zornitza Stark Phenotypes for gene: KCNJ1 were changed from to Bartter syndrome, type 2, MIM#241200
Intellectual disability syndromic and non-syndromic v0.542 KCNJ1 Zornitza Stark reviewed gene: KCNJ1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 2, MIM#241200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.542 KCND3 Zornitza Stark Marked gene: KCND3 as ready
Intellectual disability syndromic and non-syndromic v0.542 KCND3 Zornitza Stark Phenotypes for gene: KCND3 were changed from to Spinocerebellar ataxia 19, MIM#607346
Intellectual disability syndromic and non-syndromic v0.539 KCND3 Zornitza Stark reviewed gene: KCND3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 19, MIM#607346; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.539 KCNC3 Zornitza Stark Marked gene: KCNC3 as ready
Intellectual disability syndromic and non-syndromic v0.539 KCNC3 Zornitza Stark Phenotypes for gene: KCNC3 were changed from to Spinocerebellar ataxia 13, MIM#605259
Intellectual disability syndromic and non-syndromic v0.536 KCNC3 Zornitza Stark reviewed gene: KCNC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 13, MIM#605259; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.536 KARS Zornitza Stark Marked gene: KARS as ready
Intellectual disability syndromic and non-syndromic v0.536 KARS Zornitza Stark Gene: kars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.536 KARS Zornitza Stark Classified gene: KARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.536 KARS Zornitza Stark Gene: kars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.535 KARS Zornitza Stark gene: KARS was added
gene: KARS was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: KARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KARS were set to 26741492; 31618474; 28887846; 25330800; 29615062; 30252186; 28496994
Phenotypes for gene: KARS were set to Combined mitochondrial oxidative phosphorylation deficiency; epilepsy; intellectual disability; microcephaly
Review for gene: KARS was set to GREEN
gene: KARS was marked as current diagnostic
Added comment: Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.526 TRRAP Chirag Patel commented on gene: TRRAP: 31 unrelated patients with global developmental delay and variably impaired intellectual development associated with de novo heterozygous mutations of TRRAP.
Intellectual disability syndromic and non-syndromic v0.524 TRMT1 Chirag Patel edited their review of gene: TRMT1: Added comment: 4 families reported:
-1 consanguineous Iranian family with 5 individuals with nonsyndromic moderate to severe impaired intellectual development.
-1 consanguineous Iranian family with 3 adult brothers with global developmental delay and moderately delayed intellectual development
-2 unrelated Pakistani families with 4 patients with impaired intellectual development.
All with homozygous mutations in the TRMT1 gene which segregated with the disorder in the families, but functional studies of the variants were not performed.; Changed publications: PMID: 30289604, 26308914, 21937992
Intellectual disability syndromic and non-syndromic v0.524 TRMT1 Chirag Patel Source Genetic Health Queensland was removed from TRMT1.
Source Expert list was added to TRMT1.
Mode of inheritance for gene TRMT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRMT1 were changed from to Mental retardation, autosomal recessive 68; OMIM #618302
Publications for gene TRMT1 were changed from PMID: 30289604; 26308914 to PMID: 30289604; 26308914
Intellectual disability syndromic and non-syndromic v0.523 TRMT1 Chirag Patel reviewed gene: TRMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30289604, 26308914; Phenotypes: Mental retardation, autosomal recessive 68, OMIM #618302; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.518 TTR Chirag Patel Source Genetic Health Queensland was removed from TTR.
Source Expert list was added to TTR.
Mode of inheritance for gene TTR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TTR were changed from to Amyloidosis, hereditary, transthyretin-related, OMIM #105210; Carpal tunnel syndrome, familial; OMIM #115430
Intellectual disability syndromic and non-syndromic v0.517 TTR Chirag Patel reviewed gene: TTR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, hereditary, transthyretin-related, OMIM #105210, Carpal tunnel syndrome, familial, OMIM #115430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.515 TUFM Chirag Patel edited their review of gene: TUFM: Added comment: Developmental regression seen as part of mitochondrial disorder - 3 families

1 patient with rapidly progressive encephalopathy and homozygous missense mutation in the TUFM gene. No functional studies.

2 families with 2 children each with COXPD4 and biallelic mutations in the TUFM gene. The mutations segregated with the disorder in the families. Complementation with wildtype TUFM restored the complex I and IV assembly and complex IV activity levels in fibroblasts from 1 of the patients.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.513 KANK1 Zornitza Stark Marked gene: KANK1 as ready
Intellectual disability syndromic and non-syndromic v0.509 ACTA1 Zornitza Stark Marked gene: ACTA1 as ready
Intellectual disability syndromic and non-syndromic v0.505 ABCG5 Zornitza Stark Marked gene: ABCG5 as ready
Intellectual disability syndromic and non-syndromic v0.502 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Intellectual disability syndromic and non-syndromic v0.499 IYD Zornitza Stark Marked gene: IYD as ready
Intellectual disability syndromic and non-syndromic v0.496 ITCH Zornitza Stark Marked gene: ITCH as ready
Intellectual disability syndromic and non-syndromic v0.492 IREB2 Zornitza Stark Marked gene: IREB2 as ready
Intellectual disability syndromic and non-syndromic v0.491 IREB2 Zornitza Stark gene: IREB2 was added
gene: IREB2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Literature
Mode of inheritance for gene: IREB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IREB2 were set to 30915432; 31243445; 11175792
Phenotypes for gene: IREB2 were set to Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451
Review for gene: IREB2 was set to GREEN
Added comment: Two affected individuals from unrelated families with functional evidence including concordant phenotype in mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.490 INS Zornitza Stark Marked gene: INS as ready
Intellectual disability syndromic and non-syndromic v0.487 IMPA1 Zornitza Stark Marked gene: IMPA1 as ready
Intellectual disability syndromic and non-syndromic v0.487 IMPA1 Zornitza Stark Phenotypes for gene: IMPA1 were changed from to Mental retardation, autosomal recessive 59, MIM#617323
Intellectual disability syndromic and non-syndromic v0.483 IMPA1 Zornitza Stark reviewed gene: IMPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26416544, 30616629; Phenotypes: Mental retardation, autosomal recessive 59, MIM#617323; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.483 IMMP2L Zornitza Stark Marked gene: IMMP2L as ready
Intellectual disability syndromic and non-syndromic v0.479 IFT27 Zornitza Stark Marked gene: IFT27 as ready
Intellectual disability syndromic and non-syndromic v0.476 IFT27 Zornitza Stark Phenotypes for gene: IFT27 were changed from to Bardet-Biedl syndrome 19, MIM#615996
Intellectual disability syndromic and non-syndromic v0.473 IFT27 Zornitza Stark reviewed gene: IFT27: Rating: GREEN; Mode of pathogenicity: None; Publications: 24488770, 30761183; Phenotypes: Bardet-Biedl syndrome 19, MIM#615996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.473 RNF135 Chirag Patel Added comment: Comment on list classification: d/w Z.Stark - see review
Intellectual disability syndromic and non-syndromic v0.472 MYMK Chirag Patel Added comment: Comment on list classification: r/v with Dr Stark - not ID gene.
Intellectual disability syndromic and non-syndromic v0.471 UQCRQ Chirag Patel Added comment: Comment on list classification: r/v with Z.Stark - one family and no reports >10 years.
Intellectual disability syndromic and non-syndromic v0.470 VPS37A Chirag Patel Added comment: Comment on list classification: r/v with Z.Stark - 2 families with functional data.
Intellectual disability syndromic and non-syndromic v0.469 WASHC4 Chirag Patel Added comment: Comment on list classification: r/v with Z.Stark - single family with limited functional evidence
Intellectual disability syndromic and non-syndromic v0.468 WASHC5 Chirag Patel Added comment: Comment on list classification: reviewed with Z.Stark - one family with founder mutation
Intellectual disability syndromic and non-syndromic v0.467 ZNF423 Chirag Patel Added comment: Comment on list classification: reviewed with Zornitza stark - single family only.
Intellectual disability syndromic and non-syndromic v0.459 MYMK Chirag Patel Source Genetic Health Queensland was removed from MYMK.
Source Expert list was added to MYMK.
Mode of inheritance for gene MYMK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYMK were changed from to Carey-Fineman-Ziter syndrome; OMIM #254940
Intellectual disability syndromic and non-syndromic v0.458 MYMK Chirag Patel reviewed gene: MYMK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Carey-Fineman-Ziter syndrome, OMIM #254940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.457 MYH3 Chirag Patel Source Genetic Health Queensland was removed from MYH3.
Source Expert list was added to MYH3.
Mode of inheritance for gene MYH3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: MYH3 were changed from to Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM #193700; Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM #618436; Contractures, pterygia, and variable skeletal fusions syndrome 1A, OMIM #178110; Contractures, pterygia, and variable skeletal fusions syndrome 1B, OMIM #618469
Intellectual disability syndromic and non-syndromic v0.456 MYH3 Chirag Patel reviewed gene: MYH3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM #193700, Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM #618436, Contractures, pterygia, and variable skeletal fusions syndrome 1A, OMIM #178110, Contractures, pterygia, and variable skeletal fusions syndrome 1B, OMIM #618469; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.454 MTO1 Chirag Patel edited their review of gene: MTO1: Added comment: ID is seen as part of this mitochondrial disorder - >35 families reported; Changed publications: PMID: 26061759, 29331171, 23929671
Intellectual disability syndromic and non-syndromic v0.452 MTMR2 Chirag Patel Source Genetic Health Queensland was removed from MTMR2.
Source Expert list was added to MTMR2.
Mode of inheritance for gene MTMR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTMR2 were changed from to Charcot-Marie-Tooth disease, type 4B1; OMIM #601382
Intellectual disability syndromic and non-syndromic v0.451 MTMR2 Chirag Patel reviewed gene: MTMR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 4B1, OMIM #601382; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.451 IFT140 Zornitza Stark Marked gene: IFT140 as ready
Intellectual disability syndromic and non-syndromic v0.449 MSH6 Chirag Patel Source Genetic Health Queensland was removed from MSH6.
Source Expert list was added to MSH6.
Mode of inheritance for gene MSH6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: MSH6 were changed from to Colorectal cancer, hereditary nonpolyposis, type 5, OMIM #614350; Mismatch repair cancer syndrome, OMIM #276300
Intellectual disability syndromic and non-syndromic v0.447 MSH6 Chirag Patel reviewed gene: MSH6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Colorectal cancer, hereditary nonpolyposis, type 5, OMIM #614350, Mismatch repair cancer syndrome, OMIM #276300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.446 MTM1 Chirag Patel Source Genetic Health Queensland was removed from MTM1.
Source Expert list was added to MTM1.
Mode of inheritance for gene MTM1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: MTM1 were changed from to Myotubular myopathy, X-linked; OMIM#310400
Intellectual disability syndromic and non-syndromic v0.445 MTM1 Chirag Patel reviewed gene: MTM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myotubular myopathy, X-linked, OMIM#310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.439 MPV17 Chirag Patel Source Genetic Health Queensland was removed from MPV17.
Source Expert list was added to MPV17.
Mode of inheritance for gene MPV17 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MPV17 were changed from to Charcot-Marie-Tooth disease, axonal, type 2EE, OMIM #618400; Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), OMIM #256810
Publications for gene MPV17 were changed from PMID: 22593919 to PMID: 22593919
Intellectual disability syndromic and non-syndromic v0.438 MPV17 Chirag Patel reviewed gene: MPV17: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22593919; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2EE, OMIM #618400, Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), OMIM #256810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.438 IBA57 Zornitza Stark Marked gene: IBA57 as ready
Intellectual disability syndromic and non-syndromic v0.435 MPZ Chirag Patel Source Genetic Health Queensland was removed from MPZ.
Source Expert list was added to MPZ.
Mode of inheritance for gene MPZ was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MPZ were changed from to Various CMT types
Intellectual disability syndromic and non-syndromic v0.434 MPZ Chirag Patel reviewed gene: MPZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Various CMT types; 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 v0.431 MNX1 Chirag Patel Source Genetic Health Queensland was removed from MNX1.
Source Expert list was added to MNX1.
Mode of inheritance for gene MNX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MNX1 were changed from to Currarino syndrome; OMIM #176450
Intellectual disability syndromic and non-syndromic v0.430 MNX1 Chirag Patel reviewed gene: MNX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Currarino syndrome, OMIM #176450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.426 MID2 Chirag Patel Source Genetic Health Queensland was removed from MID2.
Source Expert list was added to MID2.
Mode of inheritance for gene MID2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: MID2 were changed from to ?Mental retardation, X-linked 101; OMIM#300928
Publications for gene MID2 were changed from PubMed: 24115387 to PubMed: 24115387
Intellectual disability syndromic and non-syndromic v0.425 MID2 Chirag Patel reviewed gene: MID2: Rating: RED; Mode of pathogenicity: None; Publications: PubMed: 24115387; Phenotypes: ?Mental retardation, X-linked 101, OMIM#300928; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.420 MFN2 Chirag Patel Source Genetic Health Queensland was removed from MFN2.
Source Expert list was added to MFN2.
Mode of inheritance for gene MFN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: MFN2 were changed from to Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087; Hereditary motor and sensory neuropathy VIA, OMIM #601152
Intellectual disability syndromic and non-syndromic v0.419 MFN2 Chirag Patel reviewed gene: MFN2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM #609260, Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM #617087, Hereditary motor and sensory neuropathy VIA, OMIM #601152; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.419 METTL23 Chirag Patel Source Genetic Health Queensland was removed from METTL23.
Source Expert list was added to METTL23.
Mode of inheritance for gene METTL23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: METTL23 were changed from to Mental retardation, autosomal recessive 44; OMIM#615942
Publications for gene METTL23 were changed from PubMed: 24501276; 24626631 to PubMed: 24501276; 24626631
Intellectual disability syndromic and non-syndromic v0.418 METTL23 Chirag Patel reviewed gene: METTL23: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 24501276, 24626631; Phenotypes: Mental retardation, autosomal recessive 44, OMIM#615942; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.416 MEGF8 Chirag Patel Source Genetic Health Queensland was removed from MEGF8.
Source Expert list was added to MEGF8.
Mode of inheritance for gene MEGF8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MEGF8 were changed from to Carpenter syndrome 2; OMIM #614976
Intellectual disability syndromic and non-syndromic v0.415 MEGF8 Chirag Patel reviewed gene: MEGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 3993675; Phenotypes: Carpenter syndrome 2, OMIM #614976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.413 MARS2 Chirag Patel Classified gene: MARS2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.413 MARS2 Chirag Patel Gene: mars2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.412 MARS2 Chirag Patel Source Genetic Health Queensland was removed from MARS2.
Source Expert list was added to MARS2.
Mode of inheritance for gene MARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MARS2 were changed from to ?Combined oxidative phosphorylation deficiency 25, OMIM #616430; Spastic ataxia 3, autosomal recessive, OMIM #611390
Publications for gene MARS2 were changed from PMID: 25754315 to PMID: 25754315
Intellectual disability syndromic and non-syndromic v0.411 MARS2 Chirag Patel reviewed gene: MARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 25754315; Phenotypes: ?Combined oxidative phosphorylation deficiency 25, OMIM #616430, Spastic ataxia 3, autosomal recessive, OMIM #611390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.411 HYLS1 Zornitza Stark Marked gene: HYLS1 as ready
Intellectual disability syndromic and non-syndromic v0.408 HSPG2 Zornitza Stark Marked gene: HSPG2 as ready
Intellectual disability syndromic and non-syndromic v0.408 HSPG2 Zornitza Stark Phenotypes for gene: HSPG2 were changed from to Schwartz-Jampel syndrome, type 1, MIM#255800
Intellectual disability syndromic and non-syndromic v0.406 HSPG2 Zornitza Stark reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Schwartz-Jampel syndrome, type 1, MIM#255800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.405 MAGT1 Chirag Patel Source Genetic Health Queensland was removed from MAGT1.
Source Expert list was added to MAGT1.
Mode of inheritance for gene MAGT1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: MAGT1 were changed from to Congenital disorder of glycosylation, type Icc, OMIM #301031; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, OMIM #300853
Publications for gene MAGT1 were changed from PMID: 31036665 to PMID: 31036665
Intellectual disability syndromic and non-syndromic v0.404 MAGT1 Chirag Patel reviewed gene: MAGT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 31036665; Phenotypes: Congenital disorder of glycosylation, type Icc, OMIM #301031, Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, OMIM #300853; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.404 HOXD10 Zornitza Stark Marked gene: HOXD10 as ready
Intellectual disability syndromic and non-syndromic v0.397 HNMT Zornitza Stark Marked gene: HNMT as ready
Intellectual disability syndromic and non-syndromic v0.397 HNMT Zornitza Stark Phenotypes for gene: HNMT were changed from to Mental retardation, autosomal recessive 51, MIM#616739
Intellectual disability syndromic and non-syndromic v0.394 HNMT Zornitza Stark reviewed gene: HNMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 26206890, 30744146; Phenotypes: Mental retardation, autosomal recessive 51, MIM#616739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.394 VPS37A Chirag Patel changed review comment from: ID reported in this type of HSP in 2 families.

Zivony-Elboum et al. (2012) reported 9 patients from 2 Arab Moslem families with early-onset spastic paraplegia. Affected individuals showed developmental and motor delay during the first 2 years of life. They had unsteadiness in standing and difficulty walking. All affected children presented with spasticity in the lower limbs that progressed to the upper extremities. All had mild to moderate cognitive and speech delay.; to: ID reported in this type of HSP in 2 families.

Zivony-Elboum et al. (2012) reported 9 patients from 2 Arab Moslem families with early-onset spastic paraplegia. Affected individuals showed developmental and motor delay during the first 2 years of life. They had unsteadiness in standing and difficulty walking. All affected children presented with spasticity in the lower limbs that progressed to the upper extremities. All had mild to moderate cognitive and speech delay. Functional studied performed.
Intellectual disability syndromic and non-syndromic v0.394 HAL Zornitza Stark Marked gene: HAL as ready
Intellectual disability syndromic and non-syndromic v0.389 UCHL1 Chirag Patel Source Genetic Health Queensland was removed from UCHL1.
Source Expert list was added to UCHL1.
Mode of inheritance for gene UCHL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UCHL1 were changed from to Spastic paraplegia 79, autosomal recessive; OMIM #615491
Intellectual disability syndromic and non-syndromic v0.388 UCHL1 Chirag Patel reviewed gene: UCHL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 79, autosomal recessive, OMIM #615491; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.385 UGT1A1 Chirag Patel Source Genetic Health Queensland was removed from UGT1A1.
Source Expert list was added to UGT1A1.
Mode of inheritance for gene UGT1A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UGT1A1 were changed from to Crigler-Najjar syndrome, type I, OMIM #218800; Crigler-Najjar syndrome, type II, OMIM #606785
Intellectual disability syndromic and non-syndromic v0.384 UGT1A1 Chirag Patel reviewed gene: UGT1A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Crigler-Najjar syndrome, type I, OMIM #218800, Crigler-Najjar syndrome, type II, OMIM #606785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.382 UQCC2 Chirag Patel Source Genetic Health Queensland was removed from UQCC2.
Source Expert list was added to UQCC2.
Mode of inheritance for gene UQCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCC2 were changed from to Mitochondrial complex III deficiency, nuclear type 7; OMIM #615824
Publications for gene UQCC2 were changed from PubMed: 28804536; 24385928 to PubMed: 28804536; 24385928
Intellectual disability syndromic and non-syndromic v0.380 UQCC2 Chirag Patel reviewed gene: UQCC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 28804536, 24385928; Phenotypes: Mitochondrial complex III deficiency, nuclear type 7, OMIM #615824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.379 UQCRB Chirag Patel Source Genetic Health Queensland was removed from UQCRB.
Source Expert list was added to UQCRB.
Mode of inheritance for gene UQCRB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRB were changed from to Mitochondrial complex III deficiency, nuclear type 3; OMIM #615158
Publications for gene UQCRB were changed from PubMed: 12709789; 28604960 to PubMed: 12709789; 28604960
Intellectual disability syndromic and non-syndromic v0.378 UQCRB Chirag Patel reviewed gene: UQCRB: Rating: RED; Mode of pathogenicity: None; Publications: PubMed: 12709789, 28604960; Phenotypes: Mitochondrial complex III deficiency, nuclear type 3, OMIM #615158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.378 UQCRC2 Chirag Patel Source Genetic Health Queensland was removed from UQCRC2.
Source Expert list was added to UQCRC2.
Mode of inheritance for gene UQCRC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRC2 were changed from to Mitochondrial complex III deficiency, nuclear type 5; OMIM #615160
Intellectual disability syndromic and non-syndromic v0.376 UQCRC2 Chirag Patel reviewed gene: UQCRC2: Rating: RED; Mode of pathogenicity: None; Publications: PubMed: 28275242; Phenotypes: Mitochondrial complex III deficiency, nuclear type 5, OMIM #615160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.375 UQCRQ Chirag Patel Source Genetic Health Queensland was removed from UQCRQ.
Source Expert list was added to UQCRQ.
Mode of inheritance for gene UQCRQ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRQ were changed from to Mitochondrial complex III deficiency, nuclear type 4; OMIM #615159
Publications for gene UQCRQ were changed from PubMed: 18439546 to PubMed: 18439546
Intellectual disability syndromic and non-syndromic v0.374 UQCRQ Chirag Patel reviewed gene: UQCRQ: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 18439546; Phenotypes: Mitochondrial complex III deficiency, nuclear type 4, OMIM #615159; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.370 VARS2 Chirag Patel Source Genetic Health Queensland was removed from VARS2.
Source Expert list was added to VARS2.
Mode of inheritance for gene VARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VARS2 were changed from to Combined oxidative phosphorylation deficiency 20; OMIM #615917
Publications for gene VARS2 were changed from PubMed: 24827421; 25058219; 29137650; 29314548; 31064326 to PubMed: 24827421; 25058219; 29137650; 29314548; 31064326
Intellectual disability syndromic and non-syndromic v0.369 VARS2 Chirag Patel edited their review of gene: VARS2: Added comment: Multiple patients reported with ID, encephalopathy as part of this mitochondrial disorder.; Changed rating: GREEN; Changed publications: PubMed: 24827421, 25058219, 29137650, 29314548, 31064326
Intellectual disability syndromic and non-syndromic v0.369 VARS2 Chirag Patel reviewed gene: VARS2: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 24827421, 25058219,; Phenotypes: Combined oxidative phosphorylation deficiency 20, OMIM #615917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.369 VIPAS39 Chirag Patel Source Genetic Health Queensland was removed from VIPAS39.
Source Expert list was added to VIPAS39.
Mode of inheritance for gene VIPAS39 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VIPAS39 were changed from to Arthrogryposis, renal dysfunction, and cholestasis 2; OMIM #613404
Publications for gene VIPAS39 were changed from PMID: 20190753 to PMID: 20190753
Intellectual disability syndromic and non-syndromic v0.368 VIPAS39 Chirag Patel reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 20190753; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, OMIM #613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.368 VPS33B Chirag Patel Source Genetic Health Queensland was removed from VPS33B.
Source Expert list was added to VPS33B.
Mode of inheritance for gene VPS33B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1; OMIM #208085
Publications for gene VPS33B were changed from PMID: 31240160; 30561130 to PMID: 31240160; 30561130
Intellectual disability syndromic and non-syndromic v0.367 VPS33B Chirag Patel reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31240160, 30561130; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1, OMIM #208085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.366 VPS37A Chirag Patel Source Genetic Health Queensland was removed from VPS37A.
Source Expert list was added to VPS37A.
Mode of inheritance for gene VPS37A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS37A were changed from to Spastic paraplegia 53, autosomal recessive; OMIM #614898
Publications for gene VPS37A were changed from PMID: 22717650 to PMID: 22717650
Intellectual disability syndromic and non-syndromic v0.365 VPS37A Chirag Patel reviewed gene: VPS37A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 22717650; Phenotypes: Spastic paraplegia 53, autosomal recessive, OMIM #614898; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.360 WASHC4 Chirag Patel Source Genetic Health Queensland was removed from WASHC4.
Source Expert list was added to WASHC4.
Mode of inheritance for gene WASHC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WASHC4 were changed from to ?Mental retardation, autosomal recessive 43; OMIM #615817
Publications for gene WASHC4 were changed from PubMed: 21498477 to PubMed: 21498477
Intellectual disability syndromic and non-syndromic v0.359 WASHC4 Chirag Patel reviewed gene: WASHC4: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 21498477; Phenotypes: ?Mental retardation, autosomal recessive 43, OMIM #615817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.358 WASHC5 Chirag Patel Source Genetic Health Queensland was removed from WASHC5.
Source Expert list was added to WASHC5.
Mode of inheritance for gene WASHC5 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: WASHC5 were changed from to Spastic paraplegia 8, autosomal dominant, OMIM #603563; Ritscher-Schinzel syndrome 1; OMIM #220210
Publications for gene WASHC5 were changed from PubMed: 24065355 to PubMed: 24065355
Intellectual disability syndromic and non-syndromic v0.357 WASHC5 Chirag Patel reviewed gene: WASHC5: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 24065355; Phenotypes: Spastic paraplegia 8, autosomal dominant, OMIM #603563, Ritscher-Schinzel syndrome 1, OMIM #220210; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.354 WDR19 Chirag Patel Phenotypes for gene: WDR19 were changed from ?Short-rib thoracic dysplasia 5 with or without polydactyly; OMIM #614376; AR 3 Nephronophthisis 13 614377 AR 3 Senior-Loken syndrome 8 616307 to ?Short-rib thoracic dysplasia 5 with or without polydactyly, OMIM #614376; Nephronophthisis 13, OMIM #614377; Senior-Loken syndrome 8, OMIM#616307
Intellectual disability syndromic and non-syndromic v0.353 WDR19 Chirag Patel Source Genetic Health Queensland was removed from WDR19.
Source Expert list was added to WDR19.
Mode of inheritance for gene WDR19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR19 were changed from to ?Short-rib thoracic dysplasia 5 with or without polydactyly; OMIM #614376; AR 3 Nephronophthisis 13 614377 AR 3 Senior-Loken syndrome 8 616307
Intellectual disability syndromic and non-syndromic v0.349 WDR37 Chirag Patel gene: WDR37 was added
gene: WDR37 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: WDR37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR37 were set to PubMed: 31327508; 31327510
Phenotypes for gene: WDR37 were set to Neurooculocardiogenitourinary syndrome; OMIM #618652
Review for gene: WDR37 was set to GREEN
Added comment: Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.343 HADHB Zornitza Stark Marked gene: HADHB as ready
Intellectual disability syndromic and non-syndromic v0.341 HADH Zornitza Stark Marked gene: HADH as ready
Intellectual disability syndromic and non-syndromic v0.338 H3F3B Zornitza Stark Marked gene: H3F3B as ready
Intellectual disability syndromic and non-syndromic v0.337 H19 Zornitza Stark Marked gene: H19 as ready
Intellectual disability syndromic and non-syndromic v0.335 GYS2 Zornitza Stark Marked gene: GYS2 as ready
Intellectual disability syndromic and non-syndromic v0.332 GTF2IRD1 Zornitza Stark Marked gene: GTF2IRD1 as ready
Intellectual disability syndromic and non-syndromic v0.330 GTF2I Zornitza Stark Marked gene: GTF2I as ready
Intellectual disability syndromic and non-syndromic v0.329 GSPT2 Zornitza Stark Marked gene: GSPT2 as ready
Intellectual disability syndromic and non-syndromic v0.327 GRPR Zornitza Stark Marked gene: GRPR as ready
Intellectual disability syndromic and non-syndromic v0.326 GPSM2 Zornitza Stark Marked gene: GPSM2 as ready
Intellectual disability syndromic and non-syndromic v0.324 GPHN Zornitza Stark Marked gene: GPHN as ready
Intellectual disability syndromic and non-syndromic v0.322 GOSR2 Zornitza Stark Marked gene: GOSR2 as ready
Intellectual disability syndromic and non-syndromic v0.319 GORAB Zornitza Stark Marked gene: GORAB as ready
Intellectual disability syndromic and non-syndromic v0.317 GNE Zornitza Stark Marked gene: GNE as ready
Intellectual disability syndromic and non-syndromic v0.310 ZC3H14 Chirag Patel Source Genetic Health Queensland was removed from ZC3H14.
Source Expert list was added to ZC3H14.
Mode of inheritance for gene ZC3H14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZC3H14 were changed from to Mental retardation, autosomal recessive 56; OMIM# 617125
Publications for gene ZC3H14 were changed from PubMed: 21734151 to PubMed: 21734151
Intellectual disability syndromic and non-syndromic v0.309 ZC3H14 Chirag Patel reviewed gene: ZC3H14: Rating: AMBER; Mode of pathogenicity: None; Publications: PubMed: 21734151; Phenotypes: Mental retardation, autosomal recessive 56, OMIM# 617125; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.303 ZNF335 Chirag Patel Source Genetic Health Queensland was removed from ZNF335.
Source Expert list was added to ZNF335.
Mode of inheritance for gene ZNF335 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZNF335 were changed from to Microcephaly 10, primary, autosomal recessive; OMIM #615095
Intellectual disability syndromic and non-syndromic v0.302 ZNF335 Chirag Patel reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 23178126, 27540107, 29652087; Phenotypes: Microcephaly 10, primary, autosomal recessive, OMIM #615095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.302 ZNF41 Chirag Patel changed review comment from: Shoichet et al. (2003) described a female patient with severe nonsyndromic mental retardation and a de novo balanced translocation t(X;7)(p11.3;q11.21) in whom they cloned the DNA fragment that contained the X chromosomal and the autosomal breakpoint. In silico sequence analysis demonstrated that the ZNF41 gene was disrupted. Expression studies indicated that ZNF41 transcripts were absent in the patient cell line, suggesting that the mental disorder in this patient resulted from loss of functional ZNF41. Moreover, screening of a panel of patients with MRX led to the identification of 2 other ZNF41 mutations (314995.0001-314995.0002) that were not found in healthy control individuals. Based on their finding of the mutations in ZNF41 identified by Shoichet et al. (2003) in a total of 7 males in the NHLBI Exome Variant Server, and the additional finding of truncating ZNF41 variants in 1 male and 1 female in that database, Piton et al. (2013) classified the involvement of ZNF41 in mental retardation as highly questionable.; to: Shoichet et al. (2003) described a female patient with severe nonsyndromic mental retardation and a de novo balanced translocation t(X;7)(p11.3;q11.21) in whom they cloned the DNA fragment that contained the X chromosomal and the autosomal breakpoint. In silico sequence analysis demonstrated that the ZNF41 gene was disrupted. Expression studies indicated that ZNF41 transcripts were absent in the patient cell line, suggesting that the mental disorder in this patient resulted from loss of functional ZNF41. Screening of patients with mental retardation led to the identification of 2 other ZNF41 mutations that were not found in healthy control individuals. Based on their finding of the mutations in ZNF41 identified by Shoichet et al. (2003) in a total of 7 males in the NHLBI Exome Variant Server, and the additional finding of truncating ZNF41 variants in 1 male and 1 female in that database, Piton et al. (2013) classified the involvement of ZNF41 in mental retardation as highly questionable.
Intellectual disability syndromic and non-syndromic v0.301 ZNF423 Chirag Patel Marked gene: ZNF423 as ready
Intellectual disability syndromic and non-syndromic v0.293 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Intellectual disability syndromic and non-syndromic v0.291 GNA14 Zornitza Stark Marked gene: GNA14 as ready
Intellectual disability syndromic and non-syndromic v0.290 GLUD1 Zornitza Stark Marked gene: GLUD1 as ready
Intellectual disability syndromic and non-syndromic v0.287 GLIS3 Zornitza Stark Marked gene: GLIS3 as ready
Intellectual disability syndromic and non-syndromic v0.284 GJB1 Zornitza Stark Marked gene: GJB1 as ready
Intellectual disability syndromic and non-syndromic v0.284 GJB1 Zornitza Stark Phenotypes for gene: GJB1 were changed from to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM#302800
Intellectual disability syndromic and non-syndromic v0.282 GJB1 Zornitza Stark reviewed gene: GJB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM#302800; Mode of inheritance: Other
Intellectual disability syndromic and non-syndromic v0.282 GJA1 Zornitza Stark Marked gene: GJA1 as ready
Intellectual disability syndromic and non-syndromic v0.282 GJA1 Zornitza Stark Phenotypes for gene: GJA1 were changed from to Atrioventricular septal defect 3, MIM#600309; Craniometaphyseal dysplasia, autosomal recessive, MIM#218400; Erythrokeratodermia variabilis et progressiva 3, MIM#617525; Hypoplastic left heart syndrome 1, MIM#241550; Oculodentodigital dysplasia, MIM#164200; Oculodentodigital dysplasia, autosomal recessive, MIM#257850; Palmoplantar keratoderma with congenital alopecia, MIM#104100; Syndactyly, type III, MIM# 186100
Intellectual disability syndromic and non-syndromic v0.279 GJA1 Zornitza Stark reviewed gene: GJA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrioventricular septal defect 3, MIM#600309, Craniometaphyseal dysplasia, autosomal recessive, MIM#218400, Erythrokeratodermia variabilis et progressiva 3, MIM#617525, Hypoplastic left heart syndrome 1, MIM#241550, Oculodentodigital dysplasia, MIM#164200, Oculodentodigital dysplasia, autosomal recessive, MIM#257850, Palmoplantar keratoderma with congenital alopecia, MIM#104100, Syndactyly, type III, MIM# 186100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.279 GHR Zornitza Stark Marked gene: GHR as ready
Intellectual disability syndromic and non-syndromic v0.279 GHR Zornitza Stark Phenotypes for gene: GHR were changed from to Growth hormone insensitivity, partial, MIM#604271; Laron dwarfism, MIM#262500
Intellectual disability syndromic and non-syndromic v0.276 GHR Zornitza Stark reviewed gene: GHR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Growth hormone insensitivity, partial, MIM#604271, Laron dwarfism, MIM#262500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.276 GCSH Zornitza Stark Marked gene: GCSH as ready
Intellectual disability syndromic and non-syndromic v0.272 GCK Zornitza Stark Marked gene: GCK as ready
Intellectual disability syndromic and non-syndromic v0.269 GBE1 Zornitza Stark Marked gene: GBE1 as ready
Intellectual disability syndromic and non-syndromic v0.266 GBA2 Zornitza Stark Marked gene: GBA2 as ready
Intellectual disability syndromic and non-syndromic v0.266 GBA2 Zornitza Stark Phenotypes for gene: GBA2 were changed from to Spastic paraplegia 46, autosomal recessive, MIM#614409
Intellectual disability syndromic and non-syndromic v0.263 GBA2 Zornitza Stark reviewed gene: GBA2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 46, autosomal recessive, MIM#614409; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.263 GATA6 Zornitza Stark Marked gene: GATA6 as ready
Intellectual disability syndromic and non-syndromic v0.263 GATA6 Zornitza Stark Phenotypes for gene: GATA6 were changed from to Pancreatic agenesis and congenital heart defects, MIM#600001
Intellectual disability syndromic and non-syndromic v0.260 GATA6 Zornitza Stark reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 22158542; Phenotypes: Pancreatic agenesis and congenital heart defects, MIM#600001; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.260 GATA1 Zornitza Stark Marked gene: GATA1 as ready
Intellectual disability syndromic and non-syndromic v0.258 GALT Zornitza Stark Marked gene: GALT as ready
Intellectual disability syndromic and non-syndromic v0.256 GAD1 Zornitza Stark Marked gene: GAD1 as ready
Intellectual disability syndromic and non-syndromic v0.252 GABRG1 Zornitza Stark Marked gene: GABRG1 as ready
Intellectual disability syndromic and non-syndromic v0.251 FUT8 Zornitza Stark Marked gene: FUT8 as ready
Intellectual disability syndromic and non-syndromic v0.250 FUT8 Zornitza Stark gene: FUT8 was added
gene: FUT8 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: FUT8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FUT8 were set to 29304374
Phenotypes for gene: FUT8 were set to Congenital disorder of glycosylation with defective fucosylation 1, MIM#618005
Review for gene: FUT8 was set to GREEN
Added comment: Three unrelated individuals reported with bi-allelic variants in this gene.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.249 FTL Zornitza Stark Marked gene: FTL as ready
Intellectual disability syndromic and non-syndromic v0.249 FTL Zornitza Stark Phenotypes for gene: FTL were changed from to Neurodegeneration with brain iron accumulation 3, MIM#606159; Hyperferritinemia-cataract syndrome, MIM#600886; L-ferritin deficiency, dominant and recessive, MIM#615604
Intellectual disability syndromic and non-syndromic v0.246 FTL Zornitza Stark reviewed gene: FTL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with brain iron accumulation 3, MIM#606159, Hyperferritinemia-cataract syndrome, MIM#600886, L-ferritin deficiency, dominant and recessive, MIM#615604; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.246 FRMPD4 Zornitza Stark Marked gene: FRMPD4 as ready
Intellectual disability syndromic and non-syndromic v0.246 FRMPD4 Zornitza Stark Phenotypes for gene: FRMPD4 were changed from to Mental retardation, X-linked 104, MIM#300983
Intellectual disability syndromic and non-syndromic v0.243 FRMPD4 Zornitza Stark reviewed gene: FRMPD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25644381, 29267967; Phenotypes: Mental retardation, X-linked 104, MIM#300983; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.243 FRAS1 Zornitza Stark Marked gene: FRAS1 as ready
Intellectual disability syndromic and non-syndromic v0.241 FLVCR1 Zornitza Stark Marked gene: FLVCR1 as ready
Intellectual disability syndromic and non-syndromic v0.238 FLNB Zornitza Stark Marked gene: FLNB as ready
Intellectual disability syndromic and non-syndromic v0.238 FLNB Zornitza Stark Phenotypes for gene: FLNB were changed from to Larsen syndrome, MIM#150250
Intellectual disability syndromic and non-syndromic v0.235 FLNB Zornitza Stark reviewed gene: FLNB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Larsen syndrome, MIM#150250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.235 FGF3 Zornitza Stark Marked gene: FGF3 as ready
Intellectual disability syndromic and non-syndromic v0.235 FGF3 Zornitza Stark Phenotypes for gene: FGF3 were changed from to Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM#610706
Intellectual disability syndromic and non-syndromic v0.232 FGF3 Zornitza Stark reviewed gene: FGF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM#610706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.232 FDFT1 Zornitza Stark Marked gene: FDFT1 as ready
Intellectual disability syndromic and non-syndromic v0.230 FBXO31 Zornitza Stark Marked gene: FBXO31 as ready
Intellectual disability syndromic and non-syndromic v0.230 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from to Mental retardation, autosomal recessive 45, MIM#615979
Intellectual disability syndromic and non-syndromic v0.226 FBXO31 Zornitza Stark reviewed gene: FBXO31: Rating: RED; Mode of pathogenicity: None; Publications: 24623383; Phenotypes: Mental retardation, autosomal recessive 45, MIM#615979; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.226 FBN1 Zornitza Stark Marked gene: FBN1 as ready
Intellectual disability syndromic and non-syndromic v0.226 FBN1 Zornitza Stark Phenotypes for gene: FBN1 were changed from to Marfan syndrome, MIM#154700; Geleophysic dysplasia 2, MIM#614185; Weill-Marchesani syndrome 2, dominant, MIM#608328
Intellectual disability syndromic and non-syndromic v0.223 FBN1 Zornitza Stark reviewed gene: FBN1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Marfan syndrome, MIM#154700, Geleophysic dysplasia 2, MIM#614185, Weill-Marchesani syndrome 2, dominant, MIM#608328; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.223 FBLN5 Zornitza Stark Marked gene: FBLN5 as ready
Intellectual disability syndromic and non-syndromic v0.220 FASTKD2 Zornitza Stark Marked gene: FASTKD2 as ready
Intellectual disability syndromic and non-syndromic v0.216 FARS2 Zornitza Stark Phenotypes for gene: FARS2 were changed from to Combined oxidative phosphorylation deficiency 14, MIM#614946
Intellectual disability syndromic and non-syndromic v0.215 FARS2 Zornitza Stark Publications for gene: FARS2 were set to
Intellectual disability syndromic and non-syndromic v0.214 FARS2 Zornitza Stark Mode of inheritance for gene: FARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.213 FARS2 Zornitza Stark reviewed gene: FARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22499341, 22833457; Phenotypes: Combined oxidative phosphorylation deficiency 14, MIM#614946; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.213 FANCD2 Zornitza Stark Marked gene: FANCD2 as ready
Intellectual disability syndromic and non-syndromic v0.211 EDNRB Zornitza Stark Marked gene: EDNRB as ready
Intellectual disability syndromic and non-syndromic v0.211 EDNRB Zornitza Stark Phenotypes for gene: EDNRB were changed from to Waardenburg syndrome, type 4A, MIM#277580
Intellectual disability syndromic and non-syndromic v0.208 FAAH2 Zornitza Stark Marked gene: FAAH2 as ready
Intellectual disability syndromic and non-syndromic v0.204 FA2H Zornitza Stark Marked gene: FA2H as ready
Intellectual disability syndromic and non-syndromic v0.204 FA2H Zornitza Stark Phenotypes for gene: FA2H were changed from to Spastic paraplegia 35, autosomal recessive, MIM#612319
Intellectual disability syndromic and non-syndromic v0.201 FA2H Zornitza Stark reviewed gene: FA2H: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 35, autosomal recessive, MIM#612319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.201 EXT2 Zornitza Stark Marked gene: EXT2 as ready
Intellectual disability syndromic and non-syndromic v0.199 EXOSC8 Zornitza Stark Marked gene: EXOSC8 as ready
Intellectual disability syndromic and non-syndromic v0.199 EXOSC8 Zornitza Stark Phenotypes for gene: EXOSC8 were changed from to Pontocerebellar hypoplasia, type 1C, MIM#616081
Intellectual disability syndromic and non-syndromic v0.196 EXOSC8 Zornitza Stark reviewed gene: EXOSC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24989451, 29656927; Phenotypes: Pontocerebellar hypoplasia, type 1C, MIM#616081; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.196 EXOSC2 Zornitza Stark Marked gene: EXOSC2 as ready
Intellectual disability syndromic and non-syndromic v0.195 EXOSC2 Zornitza Stark gene: EXOSC2 was added
gene: EXOSC2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: EXOSC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC2 were set to 26843489; 31628467
Phenotypes for gene: EXOSC2 were set to Short stature, hearing loss, retinitis pigmentosa, and distinctive facies, MIM# 617763
Review for gene: EXOSC2 was set to GREEN
Added comment: Three individuals from two families, but founder mutation, some functional data.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.194 ETFDH Zornitza Stark Phenotypes for gene: ETFDH were changed from to Glutaric acidemia IIC, MIM#231680
Intellectual disability syndromic and non-syndromic v0.192 ETFDH Zornitza Stark reviewed gene: ETFDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaric acidemia IIC, MIM#231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.192 ETFB Zornitza Stark Marked gene: ETFB as ready
Intellectual disability syndromic and non-syndromic v0.192 ETFB Zornitza Stark Phenotypes for gene: ETFB were changed from to Glutaric acidemia IIB, MIM#231680
Intellectual disability syndromic and non-syndromic v0.190 ETFB Zornitza Stark reviewed gene: ETFB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaric acidemia IIB, MIM#231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.190 ETFA Zornitza Stark Phenotypes for gene: ETFA were changed from to Glutaric acidemia IIA, MIM#231680
Intellectual disability syndromic and non-syndromic v0.188 ETFA Zornitza Stark reviewed gene: ETFA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaric acidemia IIA, MIM#231680; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.188 EVC2 Zornitza Stark Marked gene: EVC2 as ready
Intellectual disability syndromic and non-syndromic v0.185 EVC Zornitza Stark Marked gene: EVC as ready
Intellectual disability syndromic and non-syndromic v0.182 ERMARD Zornitza Stark Marked gene: ERMARD as ready
Intellectual disability syndromic and non-syndromic v0.182 ERMARD Zornitza Stark Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.182 ERMARD Zornitza Stark Phenotypes for gene: ERMARD were changed from to Periventricular nodular heterotopia 6, MIM#615544
Intellectual disability syndromic and non-syndromic v0.181 ERMARD Zornitza Stark Publications for gene: ERMARD were set to
Intellectual disability syndromic and non-syndromic v0.180 ERMARD Zornitza Stark Mode of inheritance for gene: ERMARD was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.179 ERMARD Zornitza Stark Classified gene: ERMARD as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.179 ERMARD Zornitza Stark Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.178 ERMARD Zornitza Stark reviewed gene: ERMARD: Rating: RED; Mode of pathogenicity: None; Publications: 24056535, 27087860; Phenotypes: Periventricular nodular heterotopia 6, MIM#615544; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.178 ERLIN2 Zornitza Stark Phenotypes for gene: ERLIN2 were changed from to Spastic paraplegia 18, autosomal recessive, MIM#611225
Intellectual disability syndromic and non-syndromic v0.176 ERLIN2 Zornitza Stark reviewed gene: ERLIN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 18, autosomal recessive, MIM#611225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.176 ERF Zornitza Stark Marked gene: ERF as ready
Intellectual disability syndromic and non-syndromic v0.173 ERCC4 Zornitza Stark Marked gene: ERCC4 as ready
Intellectual disability syndromic and non-syndromic v0.170 EPM2A Zornitza Stark Marked gene: EPM2A as ready
Intellectual disability syndromic and non-syndromic v0.167 EOMES Zornitza Stark Marked gene: EOMES as ready
Intellectual disability syndromic and non-syndromic v0.163 EOGT Zornitza Stark Marked gene: EOGT as ready
Intellectual disability syndromic and non-syndromic v0.156 EIF2B4 Zornitza Stark Marked gene: EIF2B4 as ready
Intellectual disability syndromic and non-syndromic v0.153 EIF2B3 Zornitza Stark Marked gene: EIF2B3 as ready
Intellectual disability syndromic and non-syndromic v0.150 EIF2B2 Zornitza Stark Marked gene: EIF2B2 as ready
Intellectual disability syndromic and non-syndromic v0.147 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Intellectual disability syndromic and non-syndromic v0.144 EFNB2 Zornitza Stark Marked gene: EFNB2 as ready
Intellectual disability syndromic and non-syndromic v0.140 EDNRB Zornitza Stark reviewed gene: EDNRB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Waardenburg syndrome, type 4A, MIM#277580; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.140 EARS2 Zornitza Stark Marked gene: EARS2 as ready
Intellectual disability syndromic and non-syndromic v0.140 EARS2 Zornitza Stark Gene: ears2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.140 EARS2 Zornitza Stark Phenotypes for gene: EARS2 were changed from to Combined oxidative phosphorylation deficiency 12, MIM#614924
Intellectual disability syndromic and non-syndromic v0.139 EARS2 Zornitza Stark Publications for gene: EARS2 were set to
Intellectual disability syndromic and non-syndromic v0.138 EARS2 Zornitza Stark Mode of inheritance for gene: EARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.137 EARS2 Zornitza Stark reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22492562; Phenotypes: Combined oxidative phosphorylation deficiency 12, MIM#614924; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.137 CLIP2 Zornitza Stark Marked gene: CLIP2 as ready
Intellectual disability syndromic and non-syndromic v0.132 DYNC2H1 Zornitza Stark Marked gene: DYNC2H1 as ready
Intellectual disability syndromic and non-syndromic v0.129 DYM Zornitza Stark Marked gene: DYM as ready
Intellectual disability syndromic and non-syndromic v0.127 DUOXA2 Zornitza Stark Marked gene: DUOXA2 as ready
Intellectual disability syndromic and non-syndromic v0.124 DSE Zornitza Stark Marked gene: DSE as ready
Intellectual disability syndromic and non-syndromic v0.121 DPYS Zornitza Stark Marked gene: DPYS as ready
Intellectual disability syndromic and non-syndromic v0.119 DPP10 Zornitza Stark Marked gene: DPP10 as ready
Intellectual disability syndromic and non-syndromic v0.117 DPH1 Zornitza Stark Marked gene: DPH1 as ready
Intellectual disability syndromic and non-syndromic v0.117 DPH1 Zornitza Stark Phenotypes for gene: DPH1 were changed from to Developmental delay with short stature, dysmorphic facial features, and sparse hair, MIM#616901
Intellectual disability syndromic and non-syndromic v0.114 DPH1 Zornitza Stark reviewed gene: DPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25558065, 26220823; Phenotypes: Developmental delay with short stature, dysmorphic facial features, and sparse hair, MIM#616901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.114 DOK7 Zornitza Stark Marked gene: DOK7 as ready
Intellectual disability syndromic and non-syndromic v0.111 DOCK6 Zornitza Stark Marked gene: DOCK6 as ready
Intellectual disability syndromic and non-syndromic v0.109 DOCK4 Zornitza Stark Marked gene: DOCK4 as ready
Intellectual disability syndromic and non-syndromic v0.108 DNM1L Zornitza Stark Marked gene: DNM1L as ready
Intellectual disability syndromic and non-syndromic v0.106 DNAJC6 Zornitza Stark Marked gene: DNAJC6 as ready
Intellectual disability syndromic and non-syndromic v0.106 DNAJC6 Zornitza Stark Phenotypes for gene: DNAJC6 were changed from to Parkinson disease 19a, juvenile-onset, MIM#615528
Intellectual disability syndromic and non-syndromic v0.103 DNAJC6 Zornitza Stark reviewed gene: DNAJC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease 19a, juvenile-onset, MIM#615528; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.103 DNAJC12 Zornitza Stark Marked gene: DNAJC12 as ready
Intellectual disability syndromic and non-syndromic v0.102 DNAJC12 Zornitza Stark gene: DNAJC12 was added
gene: DNAJC12 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: DNAJC12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAJC12 were set to Hyperphenylalaninemia, mild, non-BH4-deficient, MIM#617384
Review for gene: DNAJC12 was set to GREEN
Added comment: Highly variable neurological phenotype, including ID, dystonia, parkinsonism. Treatable.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.101 DMPK Zornitza Stark Marked gene: DMPK as ready
Intellectual disability syndromic and non-syndromic v0.99 DLK1 Zornitza Stark Marked gene: DLK1 as ready
Intellectual disability syndromic and non-syndromic v0.98 DLGAP2 Zornitza Stark Marked gene: DLGAP2 as ready
Intellectual disability syndromic and non-syndromic v0.97 DLG4 Zornitza Stark Marked gene: DLG4 as ready
Intellectual disability syndromic and non-syndromic v0.96 DLAT Zornitza Stark Marked gene: DLAT as ready
Intellectual disability syndromic and non-syndromic v0.94 DISP1 Zornitza Stark Marked gene: DISP1 as ready
Intellectual disability syndromic and non-syndromic v0.91 DDX59 Zornitza Stark Marked gene: DDX59 as ready
Intellectual disability syndromic and non-syndromic v0.89 DDX59 Zornitza Stark commented on gene: DDX59: Some affected individuals are reported as having ID.
Intellectual disability syndromic and non-syndromic v0.89 DDR2 Zornitza Stark Marked gene: DDR2 as ready
Intellectual disability syndromic and non-syndromic v0.89 DDR2 Zornitza Stark Phenotypes for gene: DDR2 were changed from to Warburg-Cinotti syndrome, MIM#618175, AD; Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665, AR
Intellectual disability syndromic and non-syndromic v0.86 DDR2 Zornitza Stark reviewed gene: DDR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Warburg-Cinotti syndrome, MIM#618175, AD, Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665, AR; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.86 DDB1 Zornitza Stark Marked gene: DDB1 as ready
Intellectual disability syndromic and non-syndromic v0.85 DDB1 Zornitza Stark gene: DDB1 was added
gene: DDB1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Research
Mode of inheritance for gene: DDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DDB1 were set to Syndromic intellectual disability
Review for gene: DDB1 was set to GREEN
Added comment: High quality unpublished evidence.
Sources: Research
Intellectual disability syndromic and non-syndromic v0.84 CNTN4 Zornitza Stark Marked gene: CNTN4 as ready
Intellectual disability syndromic and non-syndromic v0.80 CYP2U1 Zornitza Stark Marked gene: CYP2U1 as ready
Intellectual disability syndromic and non-syndromic v0.80 CYP2U1 Zornitza Stark Phenotypes for gene: CYP2U1 were changed from to Spastic paraplegia 56, autosomal recessive, MIM#615030
Intellectual disability syndromic and non-syndromic v0.77 CYP2U1 Zornitza Stark reviewed gene: CYP2U1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 56, autosomal recessive, MIM#615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.77 CYFIP1 Zornitza Stark Marked gene: CYFIP1 as ready
Intellectual disability syndromic and non-syndromic v0.76 CUX2 Zornitza Stark Marked gene: CUX2 as ready
Intellectual disability syndromic and non-syndromic v0.76 CUX2 Zornitza Stark Phenotypes for gene: CUX2 were changed from to Epileptic encephalopathy, early infantile, 67, MIM#618141
Intellectual disability syndromic and non-syndromic v0.73 CUX2 Zornitza Stark reviewed gene: CUX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29630738, 29795476; Phenotypes: Epileptic encephalopathy, early infantile, 67, MIM#618141; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.73 CUBN Zornitza Stark Marked gene: CUBN as ready
Intellectual disability syndromic and non-syndromic v0.70 CTU2 Zornitza Stark Marked gene: CTU2 as ready
Intellectual disability syndromic and non-syndromic v0.69 CTU2 Zornitza Stark gene: CTU2 was added
gene: CTU2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 27480277; 26633546
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142
Review for gene: CTU2 was set to GREEN
Added comment: Multiple Saudi families reported with same homozygous variant; founder effect. Severe disorder of infancy.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.68 CTSF Zornitza Stark Marked gene: CTSF as ready
Intellectual disability syndromic and non-syndromic v0.65 CTNNA2 Zornitza Stark Marked gene: CTNNA2 as ready
Intellectual disability syndromic and non-syndromic v0.64 CTNNA2 Zornitza Stark gene: CTNNA2 was added
gene: CTNNA2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: CTNNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNA2 were set to 30013181
Phenotypes for gene: CTNNA2 were set to Cortical dysplasia, complex, with other brain malformations 9, MIM#618174
Review for gene: CTNNA2 was set to GREEN
Added comment: 13 children from three unrelated families reported, severe ID as part of the phenotype.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.63 CRTAP Zornitza Stark Marked gene: CRTAP as ready
Intellectual disability syndromic and non-syndromic v0.60 CRLF1 Zornitza Stark Marked gene: CRLF1 as ready
Intellectual disability syndromic and non-syndromic v0.57 CRKL Zornitza Stark Marked gene: CRKL as ready
Intellectual disability syndromic and non-syndromic v0.54 CPA6 Zornitza Stark Marked gene: CPA6 as ready
Intellectual disability syndromic and non-syndromic v0.50 CP Zornitza Stark Marked gene: CP as ready
Intellectual disability syndromic and non-syndromic v0.47 COX7B Zornitza Stark Marked gene: COX7B as ready
Intellectual disability syndromic and non-syndromic v0.47 COX7B Zornitza Stark Phenotypes for gene: COX7B were changed from to Linear skin defects with multiple congenital anomalies 2, MIM#300887
Intellectual disability syndromic and non-syndromic v0.44 COX7B Zornitza Stark reviewed gene: COX7B: Rating: AMBER; Mode of pathogenicity: None; Publications: 23122588; Phenotypes: Linear skin defects with multiple congenital anomalies 2, MIM#300887; Mode of inheritance: Other
Intellectual disability syndromic and non-syndromic v0.44 COX4I2 Zornitza Stark Marked gene: COX4I2 as ready
Intellectual disability syndromic and non-syndromic v0.44 COX4I2 Zornitza Stark Phenotypes for gene: COX4I2 were changed from to Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis, MIM#612714
Intellectual disability syndromic and non-syndromic v0.41 COX4I2 Zornitza Stark reviewed gene: COX4I2: Rating: RED; Mode of pathogenicity: None; Publications: 19268275, 22730437; Phenotypes: Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis, MIM#612714; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.41 COX20 Zornitza Stark Marked gene: COX20 as ready
Intellectual disability syndromic and non-syndromic v0.37 COX14 Zornitza Stark Marked gene: COX14 as ready
Intellectual disability syndromic and non-syndromic v0.33 CORO1A Zornitza Stark Marked gene: CORO1A as ready
Intellectual disability syndromic and non-syndromic v0.30 COQ9 Zornitza Stark reviewed gene: COQ9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 5, MIM#614654; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.30 COQ2 Zornitza Stark Marked gene: COQ2 as ready
Intellectual disability syndromic and non-syndromic v0.30 COQ2 Zornitza Stark Phenotypes for gene: COQ2 were changed from to Coenzyme Q10 deficiency, primary, 1, MIM#607426
Intellectual disability syndromic and non-syndromic v0.28 COQ2 Zornitza Stark reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 1, MIM#607426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.28 COL18A1 Zornitza Stark Marked gene: COL18A1 as ready
Intellectual disability syndromic and non-syndromic v0.25 CNTNAP5 Zornitza Stark Marked gene: CNTNAP5 as ready
Intellectual disability syndromic and non-syndromic v0.21 CNTNAP1 Zornitza Stark Marked gene: CNTNAP1 as ready
Intellectual disability syndromic and non-syndromic v0.18 ABCC6 Chirag Patel Marked gene: ABCC6 as ready
Intellectual disability syndromic and non-syndromic v0.18 ABCC6 Chirag Patel Added comment: Comment when marking as ready: Agree not an ID gene
Intellectual disability syndromic and non-syndromic v0.16 CHD3 Zornitza Stark Marked gene: CHD3 as ready
Intellectual disability syndromic and non-syndromic v0.15 ABAT Zornitza Stark Marked gene: ABAT as ready
Intellectual disability syndromic and non-syndromic v0.12 AAAS Zornitza Stark Marked gene: AAAS as ready
Intellectual disability syndromic and non-syndromic v0.10 CLCNKB Zornitza Stark reviewed gene: CLCNKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 18310267, 29254190; Phenotypes: Bartter syndrome, type 3, MIM#607364, Bartter syndrome, type 4b, digenic, MIM#613090; Mode of inheritance: Other
Intellectual disability syndromic and non-syndromic v0.10 CLCNKA Zornitza Stark reviewed gene: CLCNKA: Rating: GREEN; Mode of pathogenicity: None; Publications: 18310267, 29254190; Phenotypes: Bartter syndrome, type 4b, digenic, MIM#613090; Mode of inheritance: Other
Intellectual disability syndromic and non-syndromic v0.10 CHD3 Zornitza Stark gene: CHD3 was added
gene: CHD3 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to 30397230
Phenotypes for gene: CHD3 were set to Snijders Blok-Campeau syndrome, MIM#618205
Review for gene: CHD3 was set to GREEN
gene: CHD3 was marked as current diagnostic
Added comment: 35 individuals from 33 unrelated families reported with heterozygous variants in this gene.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.9 CHD1 Zornitza Stark gene: CHD1 was added
gene: CHD1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Literature
Mode of inheritance for gene: CHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD1 were set to 28866611
Phenotypes for gene: CHD1 were set to Pilarowski-Bjornsson syndrome, MIM#617682
Review for gene: CHD1 was set to GREEN
Added comment: Six unrelated individuals with heterozygous variants reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.8 KIF1BP Zornitza Stark Marked gene: KIF1BP as ready
Intellectual disability syndromic and non-syndromic v0.6 CDK6 Zornitza Stark reviewed gene: CDK6: Rating: AMBER; Mode of pathogenicity: None; Publications: 23918663; Phenotypes: Microcephaly 12, primary, autosomal recessive, MIM#616080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6 CCDC78 Zornitza Stark reviewed gene: CCDC78: Rating: AMBER; Mode of pathogenicity: None; Publications: 22818856; Phenotypes: Centronuclear myopathy 4, MIM#614807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6 CACNA1G Zornitza Stark reviewed gene: CACNA1G: Rating: GREEN; Mode of pathogenicity: None; Publications: 29878067; Phenotypes: Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits, MIM#618087; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6 CACNA1E Zornitza Stark gene: CACNA1E was added
gene: CACNA1E was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1E were set to 30343943
Phenotypes for gene: CACNA1E were set to Epileptic encephalopathy, early infantile, 69, MIM#618285
Review for gene: CACNA1E was set to GREEN
gene: CACNA1E was marked as current diagnostic
Added comment: At least 30 unrelated patients reported with heterozygous variants in this gene; primarily a seizure disorder, often with profound intellectual disability.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5 CA8 Zornitza Stark reviewed gene: CA8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 19461874; Phenotypes: Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3, MIM#613227; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5 CA2 Zornitza Stark reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5 BSND Zornitza Stark reviewed gene: BSND: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bartter syndrome, type 4a, MIM#602522; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5 BRAT1 Zornitza Stark reviewed gene: BRAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26483087, 26494257, 27282546; Phenotypes: Neurodevelopmental disorder with cerebellar atrophy and with or without seizures, MIM#618056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5 BICD2 Zornitza Stark reviewed gene: BICD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM#615290; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5 BBIP1 Zornitza Stark reviewed gene: BBIP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 24026985; Phenotypes: Bardet-Biedl syndrome 18, MIM#615995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5 B3GAT3 Zornitza Stark reviewed gene: B3GAT3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects, MIM#245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5 ATXN10 Zornitza Stark reviewed gene: ATXN10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 10, MIM#603516; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5 ATP8A2 Zornitza Stark reviewed gene: ATP8A2: Rating: ; Mode of pathogenicity: None; Publications: 22892528, 31612321; Phenotypes: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4, MIM#615268; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5 ATP6AP1 Zornitza Stark gene: ATP6AP1 was added
gene: ATP6AP1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: ATP6AP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP1 were set to 27231034
Phenotypes for gene: ATP6AP1 were set to Immunodeficiency 47, MIM#300972
Review for gene: ATP6AP1 was set to GREEN
gene: ATP6AP1 was marked as current diagnostic
Added comment: 11 males from 6 unrelated families with primarily an immunodeficiency disorder; six patients from 3 families who carried the same variant (E346K) had neurologic features, including seizures, mild intellectual disability, and behavioral abnormalities
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.4 ATP2B3 Zornitza Stark reviewed gene: ATP2B3: Rating: RED; Mode of pathogenicity: None; Publications: 22912398, 27653636; Phenotypes: Spinocerebellar ataxia, X-linked 1, MIM#302500; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.4 ATP2A2 Zornitza Stark reviewed gene: ATP2A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Darier disease, MIM#124200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4 ATAD1 Zornitza Stark gene: ATAD1 was added
gene: ATAD1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: ATAD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD1 were set to 28180185
Phenotypes for gene: ATAD1 were set to Hyperekplexia 4, MIM#618011
Review for gene: ATAD1 was set to GREEN
gene: ATAD1 was marked as current diagnostic
Added comment: Severe progressive neurological disorder, severe/profound intellectual disability is a feature
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.3 ASTN1 Zornitza Stark gene: ASTN1 was added
gene: ASTN1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: ASTN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASTN1 were set to 29706646; 27431290; 26539891
Review for gene: ASTN1 was set to GREEN
gene: ASTN1 was marked as current diagnostic
Added comment: Three families reported as part of large cohorts albeit proposing multiple novel candidate genes with minimal detail and no functional validation.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.2 ASNS Zornitza Stark reviewed gene: ASNS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Asparagine synthetase deficiency, MIM#615574; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.2 ASL Zornitza Stark reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Argininosuccinic aciduria, MIM#207900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2 ASH1L Zornitza Stark gene: ASH1L was added
gene: ASH1L was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert list
Mode of inheritance for gene: ASH1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASH1L were set to 23033978; 25961944; 28394464; 28191889; 27824329
Phenotypes for gene: ASH1L were set to Mental retardation, autosomal dominant 52, MIM#617796
Review for gene: ASH1L was set to GREEN
gene: ASH1L was marked as current diagnostic
Added comment: Multiple cases with de novo variants and intellectual disability reported as part of large cohorts identifying multiple candidate genes.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.1 ARNT2 Zornitza Stark reviewed gene: ARNT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24022475; Phenotypes: Webb-Dattani syndrome 615926; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1 ARHGAP31 Zornitza Stark reviewed gene: ARHGAP31: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Adams-Oliver syndrome 1, MIM#100300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.1 APTX Zornitza Stark reviewed gene: APTX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, MIM#208920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.1 ALS2 Zornitza Stark reviewed gene: ALS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paralysis, infantile onset ascending, MIM#607225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 ALG14 Zornitza Stark reviewed gene: ALG14: Rating: AMBER; Mode of pathogenicity: None; Publications: 30221345, 23404334; Phenotypes: Myasthenic syndrome, congenital, 15, without tubular aggregates, MIM#616227, Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 ALDOB Zornitza Stark reviewed gene: ALDOB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fructose intolerance, hereditary, MIM#229600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 AGT Zornitza Stark reviewed gene: AGT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal tubular dysgenesis, MIM#267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 AGA Zornitza Stark reviewed gene: AGA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aspartylglucosaminuria, MIM#208400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 ADAT3 Zornitza Stark reviewed gene: ADAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23620220, 26842963, 29796286; Phenotypes: Mental retardation, autosomal recessive 36, MIM#615286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 ADAMTS10 Zornitza Stark reviewed gene: ADAMTS10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Weill-Marchesani syndrome 1, recessive, MIM#277600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 ABCC6 Zornitza Stark reviewed gene: ABCC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial calcification, generalized, of infancy, 2, MIM#614473, Pseudoxanthoma elasticum, MIM#264800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 VARS2 Zornitza Stark gene: VARS2 was added
gene: VARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: VARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 SPART Zornitza Stark gene: SPART was added
gene: SPART was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: SPART was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 PARN Zornitza Stark gene: PARN was added
gene: PARN was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: PARN was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 LARS2 Zornitza Stark gene: LARS2 was added
gene: LARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: LARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 LARGE1 Zornitza Stark gene: LARGE1 was added
gene: LARGE1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: LARGE1 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 IARS Zornitza Stark gene: IARS was added
gene: IARS was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: IARS was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 HARS2 Zornitza Stark gene: HARS2 was added
gene: HARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: HARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 FAR1 Zornitza Stark gene: FAR1 was added
gene: FAR1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: FAR1 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARV1 Zornitza Stark gene: ARV1 was added
gene: ARV1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARV1 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARSB Zornitza Stark gene: ARSB was added
gene: ARSB was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARSB was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARSA Zornitza Stark gene: ARSA was added
gene: ARSA was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARSA was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARMC9 Zornitza Stark gene: ARMC9 was added
gene: ARMC9 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARMC9 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARL13B Zornitza Stark gene: ARL13B was added
gene: ARL13B was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARL13B was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARID2 Zornitza Stark gene: ARID2 was added
gene: ARID2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARID2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARCN1 Zornitza Stark gene: ARCN1 was added
gene: ARCN1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARCN1 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 AARS Zornitza Stark gene: AARS was added
gene: AARS was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: AARS was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 SMARCE1 Zornitza Stark gene: SMARCE1 was added
gene: SMARCE1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: SMARCE1 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 SMARCB1 Zornitza Stark gene: SMARCB1 was added
gene: SMARCB1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: SMARCB1 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 SMARCA4 Zornitza Stark gene: SMARCA4 was added
gene: SMARCA4 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: SMARCA4 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 SMARCA2 Zornitza Stark gene: SMARCA2 was added
gene: SMARCA2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: SMARCA2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 SARS2 Zornitza Stark gene: SARS2 was added
gene: SARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: SARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 RARS2 Zornitza Stark gene: RARS2 was added
gene: RARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: RARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 RARB Zornitza Stark gene: RARB was added
gene: RARB was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: RARB was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 QARS Zornitza Stark gene: QARS was added
gene: QARS was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: QARS was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 PRKAR1A Zornitza Stark gene: PRKAR1A was added
gene: PRKAR1A was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: PRKAR1A was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 MARS2 Zornitza Stark gene: MARS2 was added
gene: MARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: MARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 LARP7 Zornitza Stark gene: LARP7 was added
gene: LARP7 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: LARP7 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 FARS2 Zornitza Stark gene: FARS2 was added
gene: FARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: FARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ERMARD Zornitza Stark gene: ERMARD was added
gene: ERMARD was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ERMARD was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 EARS2 Zornitza Stark gene: EARS2 was added
gene: EARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: EARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 DARS2 Zornitza Stark gene: DARS2 was added
gene: DARS2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: DARS2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 DARS Zornitza Stark gene: DARS was added
gene: DARS was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: DARS was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARX Zornitza Stark gene: ARX was added
gene: ARX was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARX was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARSE Zornitza Stark gene: ARSE was added
gene: ARSE was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARSE was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARNT2 Zornitza Stark gene: ARNT2 was added
gene: ARNT2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARNT2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARL6 Zornitza Stark gene: ARL6 was added
gene: ARL6 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARL6 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARID1B Zornitza Stark gene: ARID1B was added
gene: ARID1B was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARID1B was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARID1A Zornitza Stark gene: ARID1A was added
gene: ARID1A was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARID1A was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARHGEF9 Zornitza Stark gene: ARHGEF9 was added
gene: ARHGEF9 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARHGEF9 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARHGEF6 Zornitza Stark gene: ARHGEF6 was added
gene: ARHGEF6 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARHGEF6 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARHGAP31 Zornitza Stark gene: ARHGAP31 was added
gene: ARHGAP31 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARHGAP31 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARG1 Zornitza Stark gene: ARG1 was added
gene: ARG1 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARG1 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ARFGEF2 Zornitza Stark gene: ARFGEF2 was added
gene: ARFGEF2 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ARFGEF2 was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 AR Zornitza Stark gene: AR was added
gene: AR was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: AR was set to Unknown
Intellectual disability syndromic and non-syndromic v0.0 ADAR Zornitza Stark gene: ADAR was added
gene: ADAR was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: ADAR was set to Unknown