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Intellectual disability v5.418 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465; 34688657; 36976648; 37892645
Intellectual disability v5.417 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465; 34688657; 36976648; 37892645
Intellectual disability v5.417 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465
Intellectual disability v5.416 COL4A3BP Arina Puzriakova Phenotypes for gene: COL4A3BP were changed from INTELLECTUAL DISABILITY to Intellectual developmental disorder, autosomal dominant 34, OMIM:616351
Intellectual disability v5.415 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962
Intellectual disability v5.414 GAN Tracy Lester reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301315; Phenotypes: Intellectual disability, developmental delay, neuropathy, hypotonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Classified gene: KCNA3 as Amber List (moderate evidence)
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:37964487 and reviewed by Gavin Ryan, 12 patients had developmental delays, of which nine patients had mild, moderate or severe intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Gene: kcna3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Intellectual disability; Developmental Delay; Epilepsy to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.412 KCNA3 Achchuthan Shanmugasundram Publications for gene: KCNA3 were set to 37964487
Intellectual disability v5.412 KCNA3 Achchuthan Shanmugasundram Publications for gene: KCNA3 were set to PMID: 37964487
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_NHS_review tag was added to gene: KCNA3.
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: KCNA3.
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram changed review comment from: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature; to: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability.

Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotypes in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Classified gene: LGI3 as Amber List (moderate evidence)
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated families and mouse model) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Gene: lgi3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.410 LGI3 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: LGI3.
Intellectual disability v5.410 LGI3 Achchuthan Shanmugasundram gene: LGI3 was added
gene: LGI3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LGI3 were set to 35948005
Phenotypes for gene: LGI3 were set to Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects, OMIM:620007
Review for gene: LGI3 was set to GREEN
Added comment: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.409 KCNA3 Gavin Ryan gene: KCNA3 was added
gene: KCNA3 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review
Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNA3 were set to PMID: 37964487
Phenotypes for gene: KCNA3 were set to Intellectual disability; Developmental Delay; Epilepsy
Penetrance for gene: KCNA3 were set to unknown
Review for gene: KCNA3 was set to GREEN
Added comment: Soldovieri et al identified 14 de novo missense variants in KCNA3 gene. The majority of individuals presented with ID, developmental delay, and epilepsy, amongst other features. Functional studies showed loss-of-function effects for some variants and possible gain-of-function for others. One of these variants has also been identified in NHS GMS WGS patient with consistent features.
Sources: Expert Review
Intellectual disability v5.409 BAZ2B Dmitrijs Rots gene: BAZ2B was added
gene: BAZ2B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: BAZ2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAZ2B were set to PMID: 31999386
Phenotypes for gene: BAZ2B were set to developmental delay, intellectual disability and autism spectrum disorder
Review for gene: BAZ2B was set to GREEN
Added comment: BAZ2B gene is intolerant to LoF variants in population (pLI=1) and PMID: 31999386 described that de novo LoF variants are statistically enriched among NDD cases & summarize 10 cases. Enough evidence for the green rating.
Sources: Literature
Intellectual disability v5.409 ABCC9 Tracy Lester reviewed gene: ABCC9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram edited their review of gene: MTSS1L: Changed phenotypes to: Intellectual developmental disorder with ocular anomalies and distinctive facial features, OMIM:620086
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram changed review comment from: Added new-gene-name tag, new approved HGNC gene symbol for MTSS1L is MTSS2.; to: New approved HGNC gene symbol for MTSS1L is MTSS2.
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram commented on gene: MTSS1L
Intellectual disability v5.409 PRODH Arina Puzriakova Phenotypes for gene: PRODH were changed from Hyperprolinemia, type I, OMIM; 239500; {Schizophrenia, susceptibility to, OMIM:4}, 600850 to Hyperprolinemia, type I, OMIM:239500; {Schizophrenia, susceptibility to, OMIM:4}, 600850
Intellectual disability v5.408 PRICKLE1 Arina Puzriakova Phenotypes for gene: PRICKLE1 were changed from Progressive myoclonic epilepsy 1B OMIM:612437; epilepsy, progressive myoclonic, 1B MONDO:0012904 to Epilepsy, progressive myoclonic 1B, OMIM:612437
Intellectual disability v5.407 PRX Arina Puzriakova Phenotypes for gene: PRX were changed from Dejerine-Sottas disease, 145900; Charcot-Marie-Tooth disease, type 4F, 614895 to Charcot-Marie-Tooth disease, type 4F, OMIM:614895; Dejerine-Sottas disease, OMIM:145900
Intellectual disability v5.406 MTOR Sarah Leigh Publications for gene: MTOR were set to 26542245; 27830187; 25851998; 28892148; DOI: 10.4137/JGE.S12583; 27159400
Intellectual disability v5.405 DHX37 Tracy Lester reviewed gene: DHX37: Rating: GREEN; Mode of pathogenicity: None; Publications: 26539891, 31256877, 35982159; Phenotypes: Intellectual disability, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v5.405 FAM111A Achchuthan Shanmugasundram Tag Q4_23_expert_review tag was added to gene: FAM111A.
Intellectual disability v5.405 ACBD6 Arina Puzriakova Classified gene: ACBD6 as Amber List (moderate evidence)
Intellectual disability v5.405 ACBD6 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v5.405 ACBD6 Arina Puzriakova Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.404 ACBD6 Arina Puzriakova Publications for gene: ACBD6 were set to 21937992; 32108178
Intellectual disability v5.403 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.402 ACBD6 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: ACBD6.
Intellectual disability v5.402 ACBD6 Arina Puzriakova edited their review of gene: ACBD6: Added comment: - PMID: 21937992 (2011) - single individuals with a p.G22fs variant in the ACBD6 gene, presenting with mild ID, microcephaly, facial dysmorphism, spasticity. Limited additional information.

- PMID: 32108178 (2020) - two unrelated individuals with neurodevelopmental disorder (moderate ID is noted but otherwise limited clinical information) and carrying homozygous LoF variants in the ACBD6 gene (1 frameshift, 1 canonical splice). One individual also carried an allelic homozygous variant in the PRDX6 gene (unlikely but unknown disease consequence). Skin-derived patient fibroblasts showed reduced ACBD6 expression and N-myristoylation deficiency.

- PMID: 36457943 (2023) - two Thai siblings presenting with profound ID, morbid obesity, pancytopenia with severe recurrent infections, diabetes mellitus, cirrhosis, and renal failure, leading to deaths in their early 30s. Sequencing showed a novel homozygous single bp duplication (c.360dup; p.Leu121Thrfs*27) in the ACBD6 gene. Parents were heterozygous carriers.

- PMID: 37951597 (2023) - 45 previously undiagnosed individuals from 28 families with a neurodevelopmental syndrome including a complex and progressive movement disorder phenotype. Cardinal clinical features include moderate-to-severe GDD/ID (45/45), facial dysmorphism (38/40), HC <2nd percentile (21/31), weight >50th percentile (20/34), mild cerebellar ataxia (35/41), limb spasticity/hypertonia (31/41), gait abnormalities (33/35), dystonia (30/32) and variable epilepsy (13/29).

Homozygous ACBD6 variants were identified by WES in all cases, including 18 predicted LoF, 1 missense and 1 inframe insertion. Knockout studies in zebrafish recapitulate clinical features reported in patients such as movement disorders, seizures, and facial dysmorphology, while inactivation of acbd6 in X. tropicalis predominantly caused embryo death while surviving tadpoles demonstrated microcephaly, reduced movement, eye abnormalities, and brain structure differences.; Changed rating: GREEN; Changed publications to: 21937992, 32108178, 36457943, 37951597; Changed phenotypes to: Neurodevelopmental disorder, MONDO:0700092; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.402 ACBD6 Arina Puzriakova Added comment: Comment on publications: PMID: 32108178 (2020) paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.402 ACBD6 Arina Puzriakova Publications for gene: ACBD6 were set to 21937992; 32108178
Intellectual disability v5.401 KIRREL3 Dmitrijs Rots reviewed gene: KIRREL3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37605258; Phenotypes: NDD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.401 ACBD6 Sarah Leigh Classified gene: ACBD6 as Amber List (moderate evidence)
Intellectual disability v5.401 ACBD6 Sarah Leigh Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.401 ACBD6 Sarah Leigh Classified gene: ACBD6 as Amber List (moderate evidence)
Intellectual disability v5.401 ACBD6 Sarah Leigh Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.400 ACBD6 Sarah Leigh edited their review of gene: ACBD6: Added comment: ACBD6 variants have not been associated with a phenotype in OMIM, and as an autosomal recessive condition with Limited strength in Gen2Phen. Three variants have been reported in three unrelated cases with intellectual disability, however, in one of these carriers the ACBD6 variant was allelic with PRDX6 gene c.136del; p.(ValCysfs*23), therefore the contribution of the ACBD6 variant to intellectual disability is uncertain in this case (PMID: 21937992, 32108178).; Changed rating: AMBER
Intellectual disability v5.400 ACBD6 Sarah Leigh Publications for gene: ACBD6 were set to 21937992
Intellectual disability v5.399 RPL10 Achchuthan Shanmugasundram Phenotypes for gene: RPL10 were changed from Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998 to Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998
Intellectual disability v5.399 RPL10 Achchuthan Shanmugasundram Phenotypes for gene: RPL10 were changed from Mental retardation, X-linked, syndromic, 35, 300998 to Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998
Intellectual disability v5.398 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788; 25316788; 25316788; 35876338
Intellectual disability v5.398 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788; 25316788; 25316788; 35876338
Intellectual disability v5.398 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788; 25316788; 25316788; 35876338
Intellectual disability v5.397 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788; 25316788; 25316788; 35876338
Intellectual disability v5.397 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788
Intellectual disability v5.396 RPL10 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Sarah Leigh and Dmitrijs Rots, all the cases reported previously in literature and recently in PMID:35876338 were males with hemizygous RPL10 variants. The females were carriers and showed fully skewed X inactivation of the mutation-bearing X chromosomes.

In addition, this gene has been associated with relevant phenotypes in both OMIM (MIM #300998) and Gene2Phenotype (with 'definitive' rating on the DD panel). The MOI has been recorded as 'X-linked recessive' in OMIM.

The MOI should therefore be updated from 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' to 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' in the next GMS review.
Intellectual disability v5.396 RPL10 Achchuthan Shanmugasundram Mode of inheritance for gene: RPL10 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.395 RPL10 Achchuthan Shanmugasundram Tag Q4_23_MOI tag was added to gene: RPL10.
Intellectual disability v5.395 RPL10 Achchuthan Shanmugasundram reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.395 RELN Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: The MOI should be updated from "BIALLELIC, autosomal or pseudoautosomal"to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are three unrelated cases with monoallelic RELN variants and intellectual disability reported in the literature.; to: Comment on mode of inheritance: The MOI should be updated from "BIALLELIC, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review as there are three unrelated cases with monoallelic RELN variants and intellectual disability reported in the literature.
Intellectual disability v5.395 RELN Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be updated from "BIALLELIC, autosomal or pseudoautosomal"to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are three unrelated cases with monoallelic RELN variants and intellectual disability reported in the literature.
Intellectual disability v5.395 RELN Achchuthan Shanmugasundram Mode of inheritance for gene: RELN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.394 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.394 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.393 RELN Achchuthan Shanmugasundram Tag Q4_23_MOI tag was added to gene: RELN.
Intellectual disability v5.393 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.393 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.393 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), 257320; LISSENCEPHALY 2 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.392 RELN Achchuthan Shanmugasundram Publications for gene: RELN were set to
Intellectual disability v5.391 RELN Achchuthan Shanmugasundram reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: 35769015; Phenotypes: Lissencephaly 2 (Norman-Roberts type), OMIM:257320, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.391 CLDN11 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.391 CLDN11 Achchuthan Shanmugasundram Classified gene: CLDN11 as Amber List (moderate evidence)
Intellectual disability v5.391 CLDN11 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated patients) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.391 CLDN11 Achchuthan Shanmugasundram Gene: cldn11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.390 CLDN11 Achchuthan Shanmugasundram Classified gene: CLDN11 as Amber List (moderate evidence)
Intellectual disability v5.390 CLDN11 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated patients) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.390 CLDN11 Achchuthan Shanmugasundram Gene: cldn11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.389 CLDN11 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CLDN11.
Intellectual disability v5.389 CLDN11 Achchuthan Shanmugasundram gene: CLDN11 was added
gene: CLDN11 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CLDN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN11 were set to 33313762
Phenotypes for gene: CLDN11 were set to Leukodystrophy, hypomyelinating, 22, OMIM:619328
Review for gene: CLDN11 was set to GREEN
Added comment: PMID:33313762 reported three unrelated individuals with early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia. These patients exhibit global developmental delay, particularly motor and speech delay. Intellectual disability was maximally mild in two of three individuals and the intelligence is in a low-normal range in third individual, although IQ testing was not performed in them.

Two different heterozygous de novo stop-loss variants were identified in these patients. One of the variants did not lead to a loss of CLDN11 expression on RNA level in fibroblasts indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein.

This gene has been associated with hypomyelinating leukodystrophy in OMIM, which includes global developmental delay and impaired intellectual development (mild) as clinical presentations. However, this gene has not yet been associated with phenotypes in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.387 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.387 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.387 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Intellectual disability v5.386 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Intellectual disability v5.386 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Intellectual disability v5.386 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Intellectual disability v5.385 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Intellectual disability v5.385 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 24075189
Intellectual disability v5.384 RARB Achchuthan Shanmugasundram Phenotypes for gene: RARB were changed from Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092 to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.384 RARB Achchuthan Shanmugasundram Phenotypes for gene: RARB were changed from Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092 to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.383 RARB Achchuthan Shanmugasundram Phenotypes for gene: RARB were changed from MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.382 COX11 Sarah Leigh Classified gene: COX11 as Amber List (moderate evidence)
Intellectual disability v5.382 COX11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.382 COX11 Sarah Leigh Gene: cox11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.381 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB 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 v5.380 COX11 Sarah Leigh commented on gene: COX11: The three unrelated case of Mitochondrial complex IV deficiency, nuclear type 23 (OMIM:620275) so far reported, all had significant cognitive impairment and 2/3 of the cases had hypotonia (PMID: 36030551;38068960).
Intellectual disability v5.380 YARS Achchuthan Shanmugasundram changed review comment from: As reviewed by Sarah Leigh, none of the previously reported cases presented with intellectual disability, although the family reported in PMID:30304524 had expressive language delay and the older brother reported in PMID:27633801 had mild delays.

As reviewed by Dmitrijs Rots, all 12 patients from six families identified with homozygous p.Arg367Trp variant had neurodevelopmental phenotype including intellectual disability. As all these families were identified with the same homozygous variant, the rating should remain amber. However, 'watchlist' tag has been added to review this gene in future with any new evidence.; to: As reviewed by Sarah Leigh, none of the previously reported cases presented with intellectual disability, although the family reported in PMID:30304524 had expressive language delay and the older brother reported in PMID:27633801 had mild delays.

As reviewed by Dmitrijs Rots, all 12 patients from six families identified with homozygous p.Arg367Trp variant had neurodevelopmental phenotype including intellectual disability. As all these families were identified with the same homozygous variant, the rating should remain amber.
Intellectual disability v5.380 YARS Achchuthan Shanmugasundram reviewed gene: YARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, OMIM:619418; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.380 COX11 Sarah Leigh Entity copied from Mitochondrial disorders v4.142
Intellectual disability v5.380 COX11 Sarah Leigh gene: COX11 was added
gene: COX11 was added to Intellectual disability - microarray and sequencing. Sources: NHS GMS,Expert Review Amber
Q4_23_promote_green tags were added to gene: COX11.
Mode of inheritance for gene: COX11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX11 were set to 36030551; 38068960
Phenotypes for gene: COX11 were set to Mitochondrial complex IV deficiency, nuclear type 23, OMIM:620275; Mitochondrial complex IV deficiency, nuclear type 23, MONDO:0859520
Intellectual disability v5.379 CLCN6 Sarah Leigh Added comment: Comment on mode of pathogenicity: PMID 33217309 reports gain of function associated with CLCN6 variants.
Intellectual disability v5.379 CLCN6 Sarah Leigh Mode of pathogenicity for gene: CLCN6 was changed from None to None
Intellectual disability v5.378 CLCN6 Sarah Leigh Classified gene: CLCN6 as Amber List (moderate evidence)
Intellectual disability v5.378 CLCN6 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.378 CLCN6 Sarah Leigh Gene: clcn6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.377 CLCN6 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: CLCN6.
Intellectual disability v5.377 CLCN6 Sarah Leigh edited their review of gene: CLCN6: Added comment: Review copied from Neuronal ceroid lipofuscinosis panel: PMID 33217309: Three unrelated families reported with recurrent GOF de novo c.1658A>G (p.Tyr553Cys) and severe developmental delay with pronounced generalized hypotonia, respiratory insufficiency, and variable neurodegeneration and diffusion restriction in cerebral peduncles, midbrain, and/or brainstem in MRI scans. Previously, monoallelic variants reported in 3 families with BPEI, but functional data/segregation not compelling. Mouse knockout model has features of NCL (Zornitza Stark (Australian Genomics), 9 Dec 2020).; Changed rating: GREEN; 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 v5.377 CLCN6 Sarah Leigh gene: CLCN6 was added
gene: CLCN6 was added to Intellectual disability - microarray and sequencing. Sources: Other
Mode of inheritance for gene: CLCN6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116; 21107136; 33217309; 16950870
Phenotypes for gene: CLCN6 were set to Neurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities OMIM:619173
Review for gene: CLCN6 was set to RED
Added comment: Sources: Other
Intellectual disability v5.376 TRIT1 Eleanor Williams Phenotypes for gene: TRIT1 were changed from Combined oxidative phosphorylation deficiency 35, OMIM:617873 to Combined oxidative phosphorylation deficiency 35, OMIM:617873; combined oxidative phosphorylation deficiency 35, MONDO:0054742
Intellectual disability v5.375 ASL Eleanor Williams Phenotypes for gene: ASL were changed from Argininosuccinic aciduria 207900 to Argininosuccinic aciduria, OMIM:207900; argininosuccinic aciduria, MONDO:0008815
Intellectual disability v5.374 COG3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there are two unrelated cases reported with biallelic COG3 variants and hence this gene should be rated amber with current evidence.; to: Comment on list classification: As reviewed by Zornitza Stark, there are two unrelated families reported with biallelic COG3 variants and hence this gene should be rated amber with current evidence.
Intellectual disability v5.374 COG3 Achchuthan Shanmugasundram Entity copied from Congenital disorders of glycosylation v4.16
Intellectual disability v5.374 COG3 Achchuthan Shanmugasundram gene: COG3 was added
gene: COG3 was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to 37711075
Phenotypes for gene: COG3 were set to Congenital disorder of glycosylation, type IIbb, OMIM:620546
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there are eight families reported with the same variant from the same Ashkenazi Jewish ancestry and the variant co-segregated with the disease in all family members.

The 'founder-effect' tag has been added as 1 in 52 Ashkenazi Jews carry the variant.; to: Comment on list classification: As reviewed by Zornitza Stark, there are eight families reported with the same variant from the same Ashkenazi Jewish ancestry and the variant co-segregated with the disease in all family members. This gene should therefore be rated amber with the current evidence.

The 'founder-effect' tag has been added as 1 in 52 Ashkenazi Jews carry the variant.
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Classified gene: SGSM3 as Amber List (moderate evidence)
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are eight families reported with the same variant from the same Ashkenazi Jewish ancestry and the variant co-segregated with the disease in all family members.

The 'founder-effect' tag has been added as 1 in 52 Ashkenazi Jews carry the variant.
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Gene: sgsm3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Classified gene: SGSM3 as No list
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are eight families reported with the same variant from the same Ashkenazi Jewish ancestry and the variant co-segregated with the disease in all family members.

The 'founder-effect' tag has been added as 1 in 52 Ashkenazi Jews carry the variant.
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Gene: sgsm3 has been removed from the panel.
Intellectual disability v5.372 SGSM3 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: SGSM3.
Intellectual disability v5.372 SGSM3 Achchuthan Shanmugasundram Phenotypes for gene: SGSM3 were changed from Neurodevelopmental disorder (MONDO:0700092), SGSM3-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.371 SGSM3 Achchuthan Shanmugasundram reviewed gene: SGSM3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.371 SHQ1 Sarah Leigh Entity copied from Childhood onset dystonia, chorea or related movement disorder v3.61
Intellectual disability v5.371 SHQ1 Sarah Leigh gene: SHQ1 was added
gene: SHQ1 was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review Amber
Q4_23_promote_green tags were added to gene: SHQ1.
Mode of inheritance for gene: SHQ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHQ1 were set to 34542157; 29178645; 36810590; 36847845; 36416405; 37475611; 36189577
Phenotypes for gene: SHQ1 were set to ?Dystonia 35, childhood-onset, OMIM:619921; dystonia 35, childhood-onset, MONDO:0030958; Neurodevelopmental disorder with dystonia and seizures, OMIM:619922; neurodevelopmental disorder with dystonia and seizures, MONDO:0859258
Intellectual disability v5.370 FBXW11 Sarah Leigh Phenotypes for gene: FBXW11 were changed from Global developmental delay; Intellectual disability; Abnormality of the eye; Abnormality of the head; Abnormality of digit; Neurodevelopmental, jaw, eye, and digital syndrome MIM#618914 to Neurodevelopmental, jaw, eye, and digital syndrome, OMIM:618914; neurodevelopmental, jaw, eye, and digital syndrome, MONDO:003005
Intellectual disability v5.369 TRPC5 Sarah Leigh changed review comment from: To date, TRPC5 variants have not been associated with a phenotype in OMIM, however, Gen2Phen lists TRPC5 as having an Limited association with the phenotype of TRPC5-related neurodevelopmental disorder. Six TRPC5 have been reported to be associated with a neurodevelopmental disorder, which has a range of phenotypic features, including intellectual disability and autism spectrum disorder (PMIDs: 36323681;33504798;28191890;23033978).; to: To date, TRPC5 variants have not been associated with a phenotype in OMIM, however, Gen2Phen lists TRPC5 as having an Limited association with the phenotype of TRPC5-related neurodevelopmental disorder. Six TRPC5 variants have been reported to be associated with a neurodevelopmental disorder, which has a range of phenotypic features, including intellectual disability and autism spectrum disorder (PMIDs: 36323681;33504798;28191890;23033978).
Intellectual disability v5.369 TRPC5 Sarah Leigh Classified gene: TRPC5 as Amber List (moderate evidence)
Intellectual disability v5.369 TRPC5 Sarah Leigh Added comment: Comment on list classification: This gene is rated amber, despite six published variants being reported in unrelated cases with a neurodevelopmental disorder, this is because it is unclear in the publications, how many of these cases actually have intellectual disability.
Intellectual disability v5.369 TRPC5 Sarah Leigh Gene: trpc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.368 TRPC5 Sarah Leigh commented on gene: TRPC5: To date, TRPC5 variants have not been associated with a phenotype in OMIM, however, Gen2Phen lists TRPC5 as having an Limited association with the phenotype of TRPC5-related neurodevelopmental disorder. Six TRPC5 have been reported to be associated with a neurodevelopmental disorder, which has a range of phenotypic features, including intellectual disability and autism spectrum disorder (PMIDs: 36323681;33504798;28191890;23033978).
Intellectual disability v5.368 TRPC5 Sarah Leigh Classified gene: TRPC5 as Amber List (moderate evidence)
Intellectual disability v5.368 TRPC5 Sarah Leigh Gene: trpc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.367 AGPAT3 Achchuthan Shanmugasundram Classified gene: AGPAT3 as Amber List (moderate evidence)
Intellectual disability v5.367 AGPAT3 Achchuthan Shanmugasundram Gene: agpat3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.366 AGPAT3 Achchuthan Shanmugasundram Classified gene: AGPAT3 as Amber List (moderate evidence)
Intellectual disability v5.366 AGPAT3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, only one family was reported so far with AGPAT3 biallelic variants and intellectual disability. In addition, functional evidence is also available, Hence, this gene should be rated amber.
Intellectual disability v5.366 AGPAT3 Achchuthan Shanmugasundram Gene: agpat3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.365 AGPAT3 Achchuthan Shanmugasundram Phenotypes for gene: AGPAT3 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.365 AGPAT3 Achchuthan Shanmugasundram Phenotypes for gene: AGPAT3 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.365 AGPAT3 Achchuthan Shanmugasundram Phenotypes for gene: AGPAT3 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.364 AGPAT3 Achchuthan Shanmugasundram Phenotypes for gene: AGPAT3 were changed from Neurodevelopmental disorder (MONDO#0700092), AGPAT3-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.363 AGPAT3 Achchuthan Shanmugasundram edited their review of gene: AGPAT3: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.363 AGPAT3 Achchuthan Shanmugasundram reviewed gene: AGPAT3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.363 SLC12A6 Arina Puzriakova Phenotypes for gene: SLC12A6 were changed from Agenesis of the corpus callosum with peripheral neuropathy, 218000 -3; AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY (ACCPN) to Agenesis of the corpus callosum with peripheral neuropathy, OMIM:218000
Intellectual disability v5.362 C20orf24 Arina Puzriakova commented on gene: C20orf24: Added new-gene-name tag, new approved HGNC gene symbol for C20orf24 is RAB5IF
Intellectual disability v5.362 C20orf24 Arina Puzriakova Classified gene: C20orf24 as Red List (low evidence)
Intellectual disability v5.362 C20orf24 Arina Puzriakova Added comment: Comment on list classification: New gene added by Hannah Knight. Biallelic LoF variant identified in a patient with craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome. Authors suggested possible low penetrance due to two relatives with heterozygous variant and cleft lip and/or palate (PMID: 35614220).

Rating Red as only a single family reported to date. In OMIM the relationship between the phenotype and gene is provisional.
Intellectual disability v5.362 C20orf24 Arina Puzriakova Gene: c20orf24 has been classified as Red List (Low Evidence).
Intellectual disability v5.361 C20orf24 Arina Puzriakova Phenotypes for gene: C20orf24 were changed from ?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2 to ?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2, OMIM:616994
Intellectual disability v5.360 C20orf24 Arina Puzriakova Tag new-gene-name tag was added to gene: C20orf24.
Intellectual disability v5.360 MTF1 Sarah Leigh changed review comment from: Comment on publications: PMID: 23033978 reports MTF1: NM_005955.2 c.333del p.(Thr112Hisfs*26) as a de novo variant in a patient with severe ID, who also carries a maternally inherited TRPC5 NM_012471.2 c.1999C>A p.(Pro667Thr) variant (tables S3 & S10).; to: Comment on publications: PMID: 23033978 reports MTF1: NM_005955.2 c.333del p.(Thr112Hisfs*26) as a de novo variant in a patient with severe ID, who also carries a maternally inherited TRPC5 NM_012471.2 c.1999C>A p.(Pro667Thr) variant (tables S3, S9 & S10).
Intellectual disability v5.360 TRPC5 Sarah Leigh Added comment: Comment on publications: PMID: 23033978 reports MTF1: NM_005955.2 c.333del p.(Thr112Hisfs*26) as a de novo variant in a patient with severe ID, who also carries a maternally inherited TRPC5 NM_012471.2 c.1999C>A p.(Pro667Thr) variant (tables S3, S9 & S10).
Intellectual disability v5.360 TRPC5 Sarah Leigh Publications for gene: TRPC5 were set to 36323681
Intellectual disability v5.359 MTF1 Sarah Leigh Added comment: Comment on publications: PMID: 23033978 reports MTF1: NM_005955.2 c.333del p.(Thr112Hisfs*26) as a de novo variant in a patient with severe ID, who also carries a maternally inherited TRPC5 NM_012471.2 c.1999C>A p.(Pro667Thr) variant (tables S3 & S10).
Intellectual disability v5.359 MTF1 Sarah Leigh Publications for gene: MTF1 were set to 26350204; 28901405; 18341605; 23033978
Intellectual disability v5.358 MTF1 Sarah Leigh Publications for gene: MTF1 were set to 26350204; 28901405; 18341605
Intellectual disability v5.357 TRPC5 Sarah Leigh Entity copied from DDG2P v3.79
Intellectual disability v5.357 TRPC5 Sarah Leigh gene: TRPC5 was added
gene: TRPC5 was added to Intellectual disability - microarray and sequencing. Sources: DD-Gene2Phenotype,Expert Review Red
Mode of inheritance for gene: TRPC5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TRPC5 were set to 36323681
Phenotypes for gene: TRPC5 were set to TRPC5-related neurodevelopmental disorder
Intellectual disability v5.356 CDK16 Sarah Leigh Classified gene: CDK16 as Amber List (moderate evidence)
Intellectual disability v5.356 CDK16 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.356 CDK16 Sarah Leigh Gene: cdk16 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.355 CDK16 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: CDK16.
Tag Q4_23_NHS_review tag was added to gene: CDK16.
Intellectual disability v5.355 CDK16 Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability, MONDO:0001071 is the phenotype listed for CDK16 in Gene2Phen (2nd January 2024)
Intellectual disability v5.355 CDK16 Sarah Leigh Phenotypes for gene: CDK16 were changed from to Intellectual disability, MONDO:0001071
Intellectual disability v5.354 CDK16 Sarah Leigh edited their review of gene: CDK16: Added comment: To date, CDK16 variants have not been associated with a phenotype in OMIM, but have a limited association with intellectual disability (ID) in Gen2Phen. Four CDK16 variants have been associated with a spectrum of phenotypic features, including ID (n= 3), autism spectrum disorder (n= 3), seizures (n= 2) and spacity (n= 2)(PMID:36323681, 31981491, 25644381).; Changed rating: GREEN
Intellectual disability v5.354 CDK16 Sarah Leigh Publications for gene: CDK16 were set to 26350204; 25644381
Intellectual disability v5.353 ACACA Sarah Leigh Tag Q4_23_NHS_review was removed from gene: ACACA.
Intellectual disability v5.353 ACACA Sarah Leigh Entity copied from Likely inborn error of metabolism - targeted testing not possible v4.83
Intellectual disability v5.353 ACACA Sarah Leigh gene: ACACA was added
gene: ACACA was added to Intellectual disability - microarray and sequencing. Sources: Expert Review Amber,Literature
Q4_23_promote_green, Q4_23_NHS_review tags were added to gene: ACACA.
Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACACA were set to 6114432; 34552920; 36709796
Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency, OMIM: 613933
Intellectual disability v5.352 DLG2 Achchuthan Shanmugasundram Tag epigenetics was removed from gene: DLG2.
Intellectual disability v5.352 DIP2B Achchuthan Shanmugasundram Tag epigenetics was removed from gene: DIP2B.
Intellectual disability v5.352 GABRQ Achchuthan Shanmugasundram Phenotypes for gene: GABRQ were changed from ASD; schizophrenia; migraine to autism spectrum disorder, MONDO:0005258; schizophrenia, MONDO:0005090; migraine disorder, MONDO:0005277
Intellectual disability v5.351 GABRQ Achchuthan Shanmugasundram Tag Schizophrenia was removed from gene: GABRQ.
Intellectual disability v5.351 FAR1 Achchuthan Shanmugasundram Tag Q2_21_expert_review was removed from gene: FAR1.
Tag Q2_21_MOI was removed from gene: FAR1.
Intellectual disability v5.351 MYH10 Achchuthan Shanmugasundram Classified gene: MYH10 as Amber List (moderate evidence)
Intellectual disability v5.351 MYH10 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v5.351 MYH10 Achchuthan Shanmugasundram Gene: myh10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.350 MYH10 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: MYH10.
Intellectual disability v5.350 MYH10 Achchuthan Shanmugasundram Phenotypes for gene: MYH10 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies
Intellectual disability v5.350 MYH10 Achchuthan Shanmugasundram Phenotypes for gene: MYH10 were changed from MYH10-related Multiple congenital anomalies, Intellectual disability to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies
Intellectual disability v5.349 MYH10 Achchuthan Shanmugasundram Publications for gene: MYH10 were set to 25356899; 25003005
Intellectual disability v5.348 MYH10 Achchuthan Shanmugasundram Mode of inheritance for gene: MYH10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.347 MYH10 Achchuthan Shanmugasundram reviewed gene: MYH10: Rating: GREEN; Mode of pathogenicity: None; Publications: 35980381; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: This gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".; to: Comment on mode of inheritance: There is sufficient evidence available for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene can be promoted to green rating at the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.; to: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. They were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder was identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.; to: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.
Intellectual disability v5.347 TEFM Achchuthan Shanmugasundram Classified gene: TEFM as Amber List (moderate evidence)
Intellectual disability v5.347 TEFM Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.347 TEFM Achchuthan Shanmugasundram Gene: tefm has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.346 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: TEFM.
Intellectual disability v5.346 TEFM Achchuthan Shanmugasundram reviewed gene: TEFM: Rating: GREEN; Mode of pathogenicity: None; Publications: 36823193; Phenotypes: Combined oxidative phosphorylation deficiency 58, OMIM:620451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.346 TEFM Achchuthan Shanmugasundram Entity copied from Mitochondrial disorders v4.116
Intellectual disability v5.346 TEFM Achchuthan Shanmugasundram gene: TEFM was added
gene: TEFM was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TEFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEFM were set to 36823193
Phenotypes for gene: TEFM were set to Combined oxidative phosphorylation deficiency 58, OMIM:620451
Intellectual disability v5.345 KMT2B Arina Puzriakova Tag Q3_23_promote_green was removed from gene: KMT2B.
Tag Q4_23_promote_green tag was added to gene: KMT2B.
Intellectual disability v5.345 KMT2B Arina Puzriakova Classified gene: KMT2B as Amber List (moderate evidence)
Intellectual disability v5.345 KMT2B Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Inclusion on this panel would also ensure this gene is included on the Paediatric disorders super panel which is appropriate for the phenotype.
Intellectual disability v5.345 KMT2B Arina Puzriakova Gene: kmt2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.344 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from Dystonia 28, childhood-onset, 617284 to Dystonia 28, childhood-onset, OMIM:617284; Intellectual developmental disorder, autosomal dominant 68, OMIM:619934
Intellectual disability v5.343 KMT2B Arina Puzriakova Publications for gene: KMT2B were set to 25529582; 27839873; 27992417; 29276005; 25405613; 29289525; 29697234; 31216378
Intellectual disability v5.342 KMT2B Arina Puzriakova Tag watchlist was removed from gene: KMT2B.
Tag Q3_23_promote_green tag was added to gene: KMT2B.
Intellectual disability v5.342 KMT2B Arina Puzriakova reviewed gene: KMT2B: Rating: ; Mode of pathogenicity: None; Publications: 33150406; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.342 NSD2 Sarah Leigh Phenotypes for gene: NSD2 were changed from Intrauterine growth retardation; Growth delay; Microcephaly; Muscular hypotonia; Neurodevelopmental delay; Intellectual disability; No OMIM number to Rauch-Steindl syndrome, OMIM:619695; Rauch-Steindl syndrome, MONDO:0859219
Intellectual disability v5.341 C20orf24 Hannah Knight gene: C20orf24 was added
gene: C20orf24 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: C20orf24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C20orf24 were set to 35614220
Phenotypes for gene: C20orf24 were set to ?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2
Added comment: HGNC Approved Gene Symbol: RAB5IF
PMID: 35614220 (2022) identified a homozygous nonsense variant (p.W25X) in a Turkish boy previously reported by PMID: 24194475 to have bilateral cleft lip, complete cleft palate, moderate to severe intellectual delay and dysmorphic features. FHx of cleft lip/cleft palate as well in relatives who were heterozygous for the reported variant
Sources: Literature
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Classified gene: CASP2 as Amber List (moderate evidence)
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are at least three unrelated families reported with biallelic CASP2 variants and intellectual disability/ global developmental delay. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Gene: casp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Classified gene: CASP2 as Amber List (moderate evidence)
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are at least three unrelated families reported with biallelic CASP2 variants and intellectual disability/ global developmental delay. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Gene: casp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Classified gene: CASP2 as Amber List (moderate evidence)
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are at least three unrelated families reported with biallelic CASP2 variants and intellectual disability/ global developmental delay. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Gene: casp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.340 CASP2 Achchuthan Shanmugasundram Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.340 CASP2 Achchuthan Shanmugasundram Phenotypes for gene: CASP2 were changed from Autosomal recessive mental retardation to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.339 CASP2 Achchuthan Shanmugasundram Publications for gene: CASP2 were set to 26350204; 24896178; 21937992
Intellectual disability v5.338 CASP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CASP2.
Intellectual disability v5.338 CASP2 Achchuthan Shanmugasundram reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37880421; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.338 ZBTB47 Sarah Leigh commented on gene: ZBTB47: The opinion of Helen Brittain (Genomics England, Clinical Fellow), was that ZBTB47 should be green on the Intellectual disability and Early onset or syndromic epilepsy panels.
Intellectual disability v5.338 ZBTB47 Sarah Leigh edited their review of gene: ZBTB47: Added comment: ZBTB47 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37743782 reports five unrelated patients with de novo missense variants in ZBTB47 (c.2039A>G, p.(Glu680Gly) in one patient and c.1429G>A, p.(Glu477Lys) in four others), with a phenotype that included developmental delay, intellectual disability, seizures, hypotonia, gait abnormalities, and variable movement abnormalities.; Changed rating: GREEN
Intellectual disability v5.338 ZBTB47 Sarah Leigh Phenotypes for gene: ZBTB47 were changed from Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related to Neurodevelopmental disorder, MONDO; 0700092
Intellectual disability v5.337 ZBTB47 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: ZBTB47.
Intellectual disability v5.337 CASP2 Dmitrijs Rots reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37880421; Phenotypes: neurodevelopmental disorder with lissencephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.337 CLEC16A Dmitrijs Rots gene: CLEC16A was added
gene: CLEC16A was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CLEC16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLEC16A were set to PMID: 36538041
Phenotypes for gene: CLEC16A were set to severe neurodevelopmental disorder including microcephaly, brain atrophy, corpus callosum dysgenesis, and growth retardation
Penetrance for gene: CLEC16A were set to Complete
Review for gene: CLEC16A was set to GREEN
Added comment: Two independent cases reported PMID: 36538041with biallelic variants and functional evidence. Sufficient for the green rating.
Sources: Literature
Intellectual disability v5.337 VCP Achchuthan Shanmugasundram Phenotypes for gene: VCP were changed from Neurodevelopmental disorder (MONDO: 0700092) to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram edited their review of gene: VCP: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: VCP.
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram Classified gene: VCP as Amber List (moderate evidence)
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence available for adding this gene with green rating in the next GMS update.
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram Gene: vcp has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.335 VCP Achchuthan Shanmugasundram reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: None; Publications: 37883978; Phenotypes: Intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.335 DPP6 Ivone Leong commented on gene: DPP6
Intellectual disability v5.335 DPP6 Ivone Leong Tag Q4_23_demote_red tag was added to gene: DPP6.
Tag Q4_23_NHS_review tag was added to gene: DPP6.
Tag Q4_23_expert_review tag was added to gene: DPP6.
Intellectual disability v5.335 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from Dyserythropoietic anemia, congenital, type II, 224100 to Dyserythropoietic anemia, congenital, type II, OMIM:224100
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Classified gene: RAP1B as Amber List (moderate evidence)
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Gene: rap1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Classified gene: RAP1B as Amber List (moderate evidence)
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Gene: rap1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.333 RAP1B Achchuthan Shanmugasundram Publications for gene: RAP1B were set to 32627184; 26280580
Intellectual disability v5.332 RAP1B Achchuthan Shanmugasundram Tag watchlist was removed from gene: RAP1B.
Tag Q4_23_promote_green tag was added to gene: RAP1B.
Intellectual disability v5.332 RAP1B Achchuthan Shanmugasundram changed review comment from: PMID:35451551 - New patient reported with mild intellectual disability, bicuspid aortic valve, dilation of aortic root and ascending aorta, hearing loss, and long‐standing thrombocytopenia with lymphopenia. A novel, missense RAP1B variant (p.Ala59Gly) has been identified in this patient. This variant is on the neighbouring amino acid to one of the previously reported variants (p.Gly60Arg). This variant is confirmed de novo and not in gnomAD; to: PMID:35451551 - New patient reported with mild intellectual disability, bicuspid aortic valve, dilation of aortic root and ascending aorta, hearing loss, and long‐standing thrombocytopenia with lymphopenia. A novel, missense RAP1B variant (p.Ala59Gly) has been identified in this patient. This variant is on the neighbouring amino acid to one of the previously reported variants (p.Gly60Arg). This variant is confirmed de novo and not in gnomAD.

This gene has been associated with relevant phenotype in Gene2Phenotype database (with 'limited' rating in the DD panel), but not yet been associated with phenotypes in OMIM.
Intellectual disability v5.332 RAP1B Achchuthan Shanmugasundram reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 35451551; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.332 DPP6 Gavin Ryan reviewed gene: DPP6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.332 SGSM3 Zornitza Stark gene: SGSM3 was added
gene: SGSM3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SGSM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGSM3 were set to 37833060
Phenotypes for gene: SGSM3 were set to Neurodevelopmental disorder (MONDO:0700092), SGSM3-related
Review for gene: SGSM3 was set to AMBER
Added comment: PMID: 37833060
- 13 patients from 8 families of Ashkenazi Jewish origin all had the same homozygous frameshift variant (c.981dup). Predicted to cause NMD. The variant co-segregated with disease in all available family members. The affected individuals displayed mild global developmental delay and mild to moderate intellectual disability. Additional features observed included hypotonia, behavioural challenges and short stature. Considered a founder variant (1 in 52 Ashkenazi Jews carry the variant). Also present in other populations but no homozygotes in gnomAD.
Sources: Literature
Intellectual disability v5.332 AGPAT3 Zornitza Stark gene: AGPAT3 was added
gene: AGPAT3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: AGPAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGPAT3 were set to 37821758
Phenotypes for gene: AGPAT3 were set to Neurodevelopmental disorder (MONDO#0700092), AGPAT3-related
Review for gene: AGPAT3 was set to AMBER
Added comment: - Single consanguineous family with four individuals with severe intellectual disability and retinitis pigmentosa
- All affected individuals were homozygous for a nonsense variant in AGPAT3, healthy unaffected individuals who were tested were heterozygous for the variant
- Overexpression of mutant transcript revealed absence of AGPAT3 protein compared to WT transcript via Western blot analysis
- KO AGPAT3 mouse demonstrated impaired neuronal migration
Sources: Literature
Intellectual disability v5.332 VCP Zornitza Stark gene: VCP was added
gene: VCP was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 37883978
Phenotypes for gene: VCP were set to Neurodevelopmental disorder (MONDO: 0700092)
Review for gene: VCP was set to GREEN
Added comment: 13 unrelated individuals with childhood onset ID/DD disorder including macrocephaly, hypotonia and dysmorphic features. Non-specific / mild MRI findings.
12 de novo - 1 inherited
Sources: Literature
Intellectual disability v5.332 ZBTB47 Sarah Leigh reviewed gene: ZBTB47: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.332 ZBTB47 Sarah Leigh Classified gene: ZBTB47 as Amber List (moderate evidence)
Intellectual disability v5.332 ZBTB47 Sarah Leigh Gene: zbtb47 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.331 MYCN Sarah Leigh Publications for gene: MYCN were set to 37710961; 21224895; 8470948; 16906565; 18671284; 15821734; 18470948
Intellectual disability v5.330 MYCN Sarah Leigh Added comment: Comment on mode of pathogenicity: Gain-of-function MYCN variants have been reported (PMID: 30573562; 37710961) where the phenotypic features are to an extent opposite the phenotype of Feingold syndrome 1 (OMIM:164280) caused by loss-of-function MYCN variants.
Intellectual disability v5.330 MYCN Sarah Leigh Mode of pathogenicity for gene: MYCN was changed from to None
Intellectual disability v5.329 MYCN Sarah Leigh Publications for gene: MYCN were set to 21224895; 8470948; 16906565; 18671284; 15821734; 18470948
Intellectual disability v5.328 MAST4 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: MAST4.
Intellectual disability v5.328 MAST4 Sarah Leigh edited their review of gene: MAST4: Added comment: MAST4 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO to date. PMID: 36910266 reports three de novo heterozygous MAST4 missense variants in four unrelated cases, with a neurodevelopmental disorder, including cognitive delay/intellectual disability and PMID: 33057194 reports four heterozygous MAST4 missense variants in four unrelated cases and a terminating variant in an additional case, from a cohort of 31,058 parent-offspring trios of individuals with developmental disorders. Between these two publications there are five missense MAST4 variants and one terminating variant. Variant c.4412C>T (p.Thr1471Ile) was seen in three unrelated cases.; Changed rating: GREEN
Intellectual disability v5.328 MAST4 Sarah Leigh Classified gene: MAST4 as Amber List (moderate evidence)
Intellectual disability v5.328 MAST4 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.328 MAST4 Sarah Leigh Gene: mast4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.327 MAST4 Sarah Leigh Classified gene: MAST4 as Amber List (moderate evidence)
Intellectual disability v5.327 MAST4 Sarah Leigh Gene: mast4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.326 RBL2 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: RBL2.
Tag Q4_23_NHS_review tag was added to gene: RBL2.
Intellectual disability v5.326 RBL2 Sarah Leigh Classified gene: RBL2 as Amber List (moderate evidence)
Intellectual disability v5.326 RBL2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.326 RBL2 Sarah Leigh Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.325 RBL2 Sarah Leigh edited their review of gene: RBL2: Added comment: RBL2 variants have been associated with Brunet-Wagner neurodevelopmental syndrome (OMIM:619690) but not with phenotype in Gen2Phen. To date six RBL2 variants have been reported in four unrelated cases of OMIM:619690 (PMIDs: 32105419; 33980986).; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.325 RBL2 Sarah Leigh Phenotypes for gene: RBL2 were changed from intellectual diability to Brunet-Wagner neurodevelopmental syndrome, OMIM:619690
Intellectual disability v5.324 RBL2 Sarah Leigh Publications for gene: RBL2 were set to 32105419; 9806916
Intellectual disability v5.323 FAM111A Sarah Leigh Tag Q4_23_demote_red tag was added to gene: FAM111A.
Tag Q4_23_NHS_review tag was added to gene: FAM111A.
Intellectual disability v5.323 FAM111A Sarah Leigh Publications for gene: FAM111A were set to 23684011; 23996431; 25529582; 37023242; 34382758
Intellectual disability v5.322 FAM111A Sarah Leigh changed review comment from: Intellectual disability is not a feature of Gracile bone dysplasia (OMIM: 602361) or Kenny-Caffey syndrome, type 2 (OMIM: 127000)(PMID: 23684011;23996431;25529582).; to: Intellectual disability is not a feature of Gracile bone dysplasia (OMIM: 602361) or Kenny-Caffey syndrome, type 2 (OMIM: 127000)(PMID: 23684011;23996431;25529582).
PMID: 34382758 reports an autosomal recessive case of Kenny-Caffey Syndrome Type 2. The proband had inherited FAM111A variants from his healthy parents (paternal heterozygous missense
variant c.976T>A (p.L326I) and maternal heterozygous
in-frame deletion variant c.1714_1716del (p.Ile572del,
rs779963813)).
Intellectual disability v5.322 FAM111A Sarah Leigh Publications for gene: FAM111A were set to 23684011; 25529582; 37023242
Intellectual disability v5.321 FAM111A Sarah Leigh reviewed gene: FAM111A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.321 FAM111A Sarah Leigh Publications for gene: FAM111A were set to 23684011
Intellectual disability v5.320 ARF3 Achchuthan Shanmugasundram Tag watchlist was removed from gene: ARF3.
Intellectual disability v5.320 ARF3 Achchuthan Shanmugasundram Classified gene: ARF3 as Amber List (moderate evidence)
Intellectual disability v5.320 ARF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.320 ARF3 Achchuthan Shanmugasundram Gene: arf3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.319 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ARF3.
Intellectual disability v5.319 ARF3 Achchuthan Shanmugasundram Publications for gene: ARF3 were set to 34346499; 36369169
Intellectual disability v5.319 ARF3 Achchuthan Shanmugasundram Publications for gene: ARF3 were set to 34346499
Intellectual disability v5.318 ARF3 Achchuthan Shanmugasundram reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36369169; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.318 RBL2 Mike Spiller reviewed gene: RBL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32105419, PMID: 33980986; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.317 KCNH5 Arina Puzriakova Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to Developmental and epileptic encephalopathy 112, OMIM:620537
Intellectual disability v5.315 DOCK8 Dmitrijs Rots reviewed gene: DOCK8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.315 MYCN Zornitza Stark edited their review of gene: MYCN: Added comment: PMID 37710961: Three individuals now reported with gain-of-function missense variants (identical variant in two individuals) and somewhat opposing phenotype cf Feingold. Clinical presentation includes megalencephaly, hypoplastic corpus callosum, postaxial polydactyly, intellectual disability and motor delay. Knock-in mouse model showed morphological manifestations in multiple tissues including digits, female reproductive system and kidney.; Changed publications to: 21224895, 8470948, 37710961; Changed phenotypes to: Feingold syndrome 1, Megalencephaly, intellectual disability, Neurodevelopmental disorder (MONDO:0700092), MYCN-related
Intellectual disability v5.315 MAST4 Zornitza Stark gene: MAST4 was added
gene: MAST4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: MAST4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST4 were set to 36910266; 33057194
Phenotypes for gene: MAST4 were set to neurodevelopmental disorder MONDO:0700092, MAST4-related
Review for gene: MAST4 was set to GREEN
Added comment: 9 individuals with de novo missense variants and ID reported altogether.

PMID: 36910266 - 4 affecteds from unrelated families, all de novo missense

2x borderline microcephaly (-2SD)
2x gross motor delay
2x dysmorphism
4x ID + seizures
3x abnormal brain MRI findings

PMID: 33057194 - 5x de novos, 4x missense + 1x PTC
Cohort of individuals with severe developmental disorder
individual phenotypic information not provided


Recurrent variants are Thr1471Ile (3x) and Ser1181Phe)
Sources: Literature
Intellectual disability v5.315 ZBTB47 Zornitza Stark gene: ZBTB47 was added
gene: ZBTB47 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB47 were set to 37743782
Phenotypes for gene: ZBTB47 were set to Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related
Review for gene: ZBTB47 was set to GREEN
Added comment: PMID 37743782:
- 5 individuals with de novo missense variants, 4/5 have a recurring p.Gly477Lys. Probands have intellectual disability (5/5), seizures (5/5), hypotonia (5/5), gait abnormalities, and variable movement abnormalities (5/5).
- Missense variants are positioned close to His and Cys residues involved in forming C2H2 zinc fingers.
- No functional studies performed
Sources: Literature
Intellectual disability v5.315 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Intellectual disability v5.315 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Intellectual disability v5.315 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Intellectual disability v5.315 ERI1 Achchuthan Shanmugasundram Classified gene: ERI1 as Amber List (moderate evidence)
Intellectual disability v5.315 ERI1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases with biallelic null ERI1 variants and mild intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.315 ERI1 Achchuthan Shanmugasundram Gene: eri1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.314 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ERI1.
Intellectual disability v5.314 ERI1 Achchuthan Shanmugasundram gene: ERI1 was added
gene: ERI1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 36208065; 37352860
Phenotypes for gene: ERI1 were set to intellectual disability, MONDO:0001071
Review for gene: ERI1 was set to GREEN
Added comment: PMID:36208065 reported a female patient with a homozygous nonsense variant in ERI1 gene and with mild intellectual disability (ID), eyelid ptosis, and anomalies in her hands and feet (brachydactyly, clinodactyly, dysplastic/short nail of halluces, brachytelephalangy, short metacarpals, and toe syndactyly).

PMID:37352860 reported eight patients from seven unrelated families with compound heterozygous variants in ERI1 gene, of which four patients had missense variants, three had null variants and one had missense and PTC variants. The patients with missense variants had a more severe severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly. The patients with null variants had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly. The patient with both missense and PTC variants had phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, and delayed motor milestones and speech and generalised hypotonia.

This gene has not yet been reported with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.313 TUBGCP2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TUBGCP2.
Intellectual disability v5.313 MMGT1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MMGT1.
Intellectual disability v5.313 MMGT1 Achchuthan Shanmugasundram commented on gene: MMGT1
Intellectual disability v5.313 HECTD4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HECTD4.
Intellectual disability v5.313 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4: The OMIM entry for this gene is OMIM:620209, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Intellectual disability v5.313 CCDC82 Achchuthan Shanmugasundram commented on gene: CCDC82: The OMIM entry for this gene is OMIM:619870, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Intellectual disability v5.313 CCDC82 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC82.
Intellectual disability v5.313 CCDC32 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:618941, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Intellectual disability v5.313 ZMYND8 Eleanor Williams commented on gene: ZMYND8
Intellectual disability v5.313 ZMYND8 Eleanor Williams Tag gene-checked tag was added to gene: ZMYND8.
Intellectual disability v5.313 TRA2B Eleanor Williams Tag gene-checked tag was added to gene: TRA2B.
Intellectual disability v5.313 TRA2B Eleanor Williams commented on gene: TRA2B
Intellectual disability v5.313 SLC32A1 Eleanor Williams commented on gene: SLC32A1
Intellectual disability v5.313 SLC32A1 Eleanor Williams Tag gene-checked tag was added to gene: SLC32A1.
Intellectual disability v5.313 SHANK1 Eleanor Williams Tag gene-checked tag was added to gene: SHANK1.
Intellectual disability v5.313 SHANK1 Eleanor Williams commented on gene: SHANK1
Intellectual disability v5.313 RBSN Eleanor Williams commented on gene: RBSN
Intellectual disability v5.313 RBSN Eleanor Williams Tag gene-checked tag was added to gene: RBSN.
Intellectual disability v5.313 POU3F2 Eleanor Williams Tag gene-checked tag was added to gene: POU3F2.
Intellectual disability v5.313 POU3F2 Eleanor Williams commented on gene: POU3F2
Intellectual disability v5.313 PLK1 Eleanor Williams Tag gene-checked tag was added to gene: PLK1.
Intellectual disability v5.313 PLK1 Eleanor Williams commented on gene: PLK1
Intellectual disability v5.313 PAN2 Eleanor Williams commented on gene: PAN2
Intellectual disability v5.313 PAN2 Eleanor Williams Tag gene-checked tag was added to gene: PAN2.
Intellectual disability v5.313 OTUD7A Eleanor Williams commented on gene: OTUD7A
Intellectual disability v5.313 OTUD7A Eleanor Williams Tag gene-checked tag was added to gene: OTUD7A.
Intellectual disability v5.313 LHX2 Eleanor Williams Tag gene-checked tag was added to gene: LHX2.
Intellectual disability v5.313 LHX2 Eleanor Williams commented on gene: LHX2
Intellectual disability v5.313 KLHL20 Eleanor Williams commented on gene: KLHL20
Intellectual disability v5.313 KLHL20 Eleanor Williams Tag gene-checked tag was added to gene: KLHL20.
Intellectual disability v5.313 KDM5A Eleanor Williams Tag gene-checked tag was added to gene: KDM5A.
Intellectual disability v5.313 KDM5A Eleanor Williams commented on gene: KDM5A
Intellectual disability v5.313 KDM2B Eleanor Williams Tag gene-checked tag was added to gene: KDM2B.
Intellectual disability v5.313 KDM2B Eleanor Williams commented on gene: KDM2B
Intellectual disability v5.313 CCDC32 Achchuthan Shanmugasundram commented on gene: CCDC32
Intellectual disability v5.313 C2orf69 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been crossed checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Intellectual disability v5.313 C2orf69 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: C2orf69.
Intellectual disability v5.313 C2orf69 Achchuthan Shanmugasundram commented on gene: C2orf69
Intellectual disability v5.313 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5
Intellectual disability v5.313 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Intellectual disability v5.313 FILIP1 Eleanor Williams Tag gene-checked tag was added to gene: FILIP1.
Intellectual disability v5.313 FILIP1 Eleanor Williams commented on gene: FILIP1
Intellectual disability v5.313 SRRM2 Arina Puzriakova Phenotypes for gene: SRRM2 were changed from SRRM2-related developmental disorder (monoallelic) to Intellectual developmental disorder, autosomal dominant 72, OMIM:620439
Intellectual disability v5.312 DDX23 Eleanor Williams Tag gene-checked tag was added to gene: DDX23.
Intellectual disability v5.312 SRRM2 Arina Puzriakova Tag gene-checked was removed from gene: SRRM2.
Intellectual disability v5.312 DDX23 Eleanor Williams commented on gene: DDX23
Intellectual disability v5.312 SCAF4 Arina Puzriakova Phenotypes for gene: SCAF4 were changed from SCAF4-related Neurodevelopmental Disorder; Intellectual disability; Seizures; Behavioural abnormalities to Fliedner-Zweier syndrome, OMIM:620511
Intellectual disability v5.311 SCAF4 Arina Puzriakova Tag gene-checked was removed from gene: SCAF4.
Intellectual disability v5.311 CTR9 Eleanor Williams Tag gene-checked tag was added to gene: CTR9.
Intellectual disability v5.311 CTR9 Eleanor Williams commented on gene: CTR9
Intellectual disability v5.311 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071; Neurooculorenal syndrome, OMIM:620305
Intellectual disability v5.310 RFX7 Arina Puzriakova Phenotypes for gene: RFX7 were changed from Intellectual disability, MONDO:0001071; Autism spectrum disorder, MONDO:0005258; Attention deficit-hyperactivity disorder, MONDO:0007743 to Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, OMIM:620330
Intellectual disability v5.309 RFX7 Arina Puzriakova Tag gene-checked was removed from gene: RFX7.
Intellectual disability v5.309 CLDN5 Eleanor Williams commented on gene: CLDN5
Intellectual disability v5.309 CLDN5 Eleanor Williams Tag gene-checked tag was added to gene: CLDN5.
Intellectual disability v5.309 AGO1 Arina Puzriakova Tag gene-checked was removed from gene: AGO1.
Intellectual disability v5.309 AGO1 Arina Puzriakova Phenotypes for gene: AGO1 were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Autism to Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, OMIM:620292
Intellectual disability v5.308 CAPRIN1 Eleanor Williams Tag gene-checked tag was added to gene: CAPRIN1.
Intellectual disability v5.308 CAPRIN1 Eleanor Williams commented on gene: CAPRIN1
Intellectual disability v5.308 SRSF1 Achchuthan Shanmugasundram Classified gene: SRSF1 as Amber List (moderate evidence)
Intellectual disability v5.308 SRSF1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (15 unrelated cases and functional evidence) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.308 SRSF1 Achchuthan Shanmugasundram Gene: srsf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.307 SRSF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: SRSF1.
Intellectual disability v5.307 SRSF1 Achchuthan Shanmugasundram gene: SRSF1 was added
gene: SRSF1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SRSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRSF1 were set to 37071997
Phenotypes for gene: SRSF1 were set to Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:620489
Review for gene: SRSF1 was set to GREEN
Added comment: There are 17 individuals from 16 different families were reported with 15 different monoallelic variants (mostly de novo) in SRSF1 gene. They were reported with a neurodevelopmental disorder mainly comprising neurological abnormalities such as intellectual disability/ developmental delay, motor delay, speech delay, and behavioural disorders and facial dysmorphisms. Intellectual disability was present in 16 of 17 individuals (3 severe, 2 moderate, 3 mild to moderate, 3 mild, 1 borderline and 4 unknown severity), while the remaining one had learning disability.

Functional testing of a subset of variants in Drosophila supported pathogenicity in most, but 2 missense variants showed no functional effect and were classified VUS.

This gene has already been associated with neurodevelopmental disorder in both OMIM (MIM #620489) and Gene2Phenotype ('limited' rating in the DD panel).
Sources: Literature
Intellectual disability v5.306 GCSH Arina Puzriakova Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to Multiple mitochondrial dysfunctions syndrome 7, OMIM:620423; Glycine encephalopathy; Transient neonatal hyperglycinemia
Intellectual disability v5.305 ZNF292 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ZNF292.
Tag Q1_23_NHS_review was removed from gene: ZNF292.
Intellectual disability v5.305 ZMYND8 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: ZMYND8.
Intellectual disability v5.305 ZMYM3 Arina Puzriakova Phenotypes for gene: ZMYM3 were changed from X-linked mental retardation to Intellectual developmental disorder, X-linked 112, OMIM:301111
Intellectual disability v5.304 ZMYM3 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ZMYM3.
Intellectual disability v5.304 WIPI2 Arina Puzriakova Phenotypes for gene: WIPI2 were changed from ?Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 to Intellectual developmental disorder with short stature and variable skeletal anomalies, OMIM:618453
Intellectual disability v5.303 WIPI2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: WIPI2.
Intellectual disability v5.303 UBAP2L Arina Puzriakova Phenotypes for gene: UBAP2L were changed from Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, OMIM:620494
Intellectual disability v5.302 UBAP2L Arina Puzriakova Tag Q1_23_promote_green was removed from gene: UBAP2L.
Intellectual disability v5.302 TRA2B Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TRA2B.
Intellectual disability v5.302 TMEM147 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: TMEM147.
Intellectual disability v5.302 TCEAL1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TCEAL1.
Intellectual disability v5.302 TAF4 Arina Puzriakova Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal dominant 73, OMIM:620450
Intellectual disability v5.301 TAF4 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TAF4.
Intellectual disability v5.301 TAF2 Arina Puzriakova Phenotypes for gene: TAF2 were changed from Mental retardation, autosomal recessive 40, 615599 to Mental retardation, autosomal recessive 40, OMIM:615599
Intellectual disability v5.300 TAF2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TAF2.
Intellectual disability v5.300 SUFU Arina Puzriakova Tag watchlist_moi was removed from gene: SUFU.
Tag Q4_22_MOI was removed from gene: SUFU.
Tag Q4_22_promote_green was removed from gene: SUFU.
Tag Q4_22_expert_review was removed from gene: SUFU.
Intellectual disability v5.300 STXBP1 Arina Puzriakova Tag Q1_23_MOI was removed from gene: STXBP1.
Intellectual disability v5.300 SLC32A1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: SLC32A1.
Intellectual disability v5.300 SHANK1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: SHANK1.
Intellectual disability v5.300 SEMA6B Arina Puzriakova Tag Q1_23_promote_green was removed from gene: SEMA6B.
Intellectual disability v5.300 SARS Arina Puzriakova Tag Q1_23_promote_green was removed from gene: SARS.
Intellectual disability v5.300 ROR2 Arina Puzriakova Tag Q4_22_demote_red was removed from gene: ROR2.
Tag Q4_22_NHS_review was removed from gene: ROR2.
Intellectual disability v5.300 ROBO1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ROBO1.
Intellectual disability v5.300 RBSN Arina Puzriakova Tag Q1_23_promote_green was removed from gene: RBSN.
Intellectual disability v5.300 PRKAR1B Arina Puzriakova Phenotypes for gene: PRKAR1B were changed from Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.299 PRKAR1B Arina Puzriakova Tag watchlist was removed from gene: PRKAR1B.
Tag Q2_23_promote_green was removed from gene: PRKAR1B.
Intellectual disability v5.299 PPFIBP1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PPFIBP1.
Intellectual disability v5.299 POU3F2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: POU3F2.
Intellectual disability v5.299 PLXNA1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PLXNA1.
Intellectual disability v5.299 PLK1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PLK1.
Intellectual disability v5.299 PAX6 Arina Puzriakova Tag Q1_23_demote_red was removed from gene: PAX6.
Tag Q1_23_NHS_review was removed from gene: PAX6.
Intellectual disability v5.299 PAN2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: PAN2.
Intellectual disability v5.299 OTUD7A Arina Puzriakova Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, intellectual disability, no OMIM# yet to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.298 OTUD7A Arina Puzriakova Tag Q2_23_promote_green was removed from gene: OTUD7A.
Intellectual disability v5.298 NUP214 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: NUP214.
Intellectual disability v5.298 MTSS1L Arina Puzriakova Phenotypes for gene: MTSS1L were changed from Global developmental delay; Intellectual disability; Ophthalmological anomalies; Microcephaly; Mild facial dysmorphisms to Intellectual developmental disorder with ocular anomalies and distinctive facial features, OMIM:620086
Intellectual disability v5.297 MTSS1L Arina Puzriakova Tag Q4_22_promote_green was removed from gene: MTSS1L.
Intellectual disability v5.297 MED11 Arina Puzriakova Phenotypes for gene: MED11 were changed from MED11-associated neurodevelopmental disorder to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, OMIM:620327
Intellectual disability v5.296 MED11 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: MED11.
Intellectual disability v5.296 MAN2C1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: MAN2C1.
Intellectual disability v5.296 LHX2 Arina Puzriakova Phenotypes for gene: LHX2 were changed from neurodevelopmental disorder to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.295 LHX2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: LHX2.
Intellectual disability v5.295 KLHL20 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: KLHL20.
Intellectual disability v5.295 KIF4A Arina Puzriakova Tag Q2_23_promote_green was removed from gene: KIF4A.
Intellectual disability v5.295 KDM5A Arina Puzriakova Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.294 KDM5A Arina Puzriakova Tag Q2_23_promote_green was removed from gene: KDM5A.
Tag Q2_23_NHS_review was removed from gene: KDM5A.
Intellectual disability v5.294 KDM2B Arina Puzriakova Tag Q2_23_promote_green was removed from gene: KDM2B.
Intellectual disability v5.294 KCNK3 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: KCNK3.
Intellectual disability v5.294 ITPR1 Arina Puzriakova Tag Q2_23_MOI was removed from gene: ITPR1.
Tag Q2_23_NHS_review was removed from gene: ITPR1.
Intellectual disability v5.294 IQSEC2 Arina Puzriakova Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1, 309530; non-syndromic X-linked intellectual disability; Rett like phenotype in males; MENTAL RETARDATION X-LINKED TYPE 1 (MRX1) to Intellectual developmental disorder, X-linked 1, OMIM:309530
Intellectual disability v5.293 IQSEC2 Arina Puzriakova Tag Q2_23_MOI was removed from gene: IQSEC2.
Intellectual disability v5.293 INTS11 Arina Puzriakova Phenotypes for gene: INTS11 were changed from Complex neurodevelopmental disorder, MONDO:0100038 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Intellectual disability v5.292 INTS11 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: INTS11.
Intellectual disability v5.292 HUWE1 Arina Puzriakova Tag Q2_23_MOI was removed from gene: HUWE1.
Intellectual disability v5.292 HIST1H4E Arina Puzriakova Tag Q1_23_promote_green was removed from gene: HIST1H4E.
Intellectual disability v5.292 HECTD4 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: HECTD4.
Intellectual disability v5.292 GRM7 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: GRM7.
Intellectual disability v5.292 GRIA1 Arina Puzriakova Tag watchlist_moi tag was added to gene: GRIA1.
Intellectual disability v5.292 GRIA1 Arina Puzriakova Tag Autism Spectrum Disorder was removed from gene: GRIA1.
Tag Q2_23_promote_green was removed from gene: GRIA1.
Intellectual disability v5.292 GCSH Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GCSH.
Intellectual disability v5.292 FRMD5 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: FRMD5.
Intellectual disability v5.292 FLNA Arina Puzriakova Tag Q2_23_demote_red was removed from gene: FLNA.
Intellectual disability v5.292 FILIP1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: FILIP1.
Intellectual disability v5.292 ENTPD1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: ENTPD1.
Intellectual disability v5.292 DPH5 Arina Puzriakova Phenotypes for gene: DPH5 were changed from DPH5-related neurodevelopmental disorder to Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, OMIM:620070
Intellectual disability v5.291 DPH5 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: DPH5.
Intellectual disability v5.291 DDX23 Arina Puzriakova Phenotypes for gene: DDX23 were changed from Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066 to Global developmental delay with speech and behavioral abnormalities, MONDO:0030995
Intellectual disability v5.290 DOHH Arina Puzriakova Phenotypes for gene: DOHH were changed from DOHH associated neurodevelopmental disorder to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066
Intellectual disability v5.289 DDX23 Arina Puzriakova Phenotypes for gene: DDX23 were changed from Global developmental delay with speech and behavioral abnormalities, MONDO:0030995 to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066
Intellectual disability v5.288 DOHH Arina Puzriakova Tag Q4_22_MOI was removed from gene: DOHH.
Tag Q4_22_promote_green was removed from gene: DOHH.
Intellectual disability v5.288 DDX23 Arina Puzriakova Phenotypes for gene: DDX23 were changed from Developmental disorder to Global developmental delay with speech and behavioral abnormalities, MONDO:0030995
Intellectual disability v5.287 DDX23 Arina Puzriakova Tag watchlist was removed from gene: DDX23.
Tag Q2_23_promote_green was removed from gene: DDX23.
Intellectual disability v5.287 CTR9 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CTR9.
Intellectual disability v5.287 CPLX1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CPLX1.
Intellectual disability v5.287 CLDN5 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: CLDN5.
Intellectual disability v5.287 CCDC82 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: CCDC82.
Intellectual disability v5.287 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures to Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures
Intellectual disability v5.287 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from AUTISM OR INTELLECTUAL DISABILITY to Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures
Intellectual disability v5.286 CAPRIN1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CAPRIN1.
Intellectual disability v5.286 C2orf69 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: C2orf69.
Intellectual disability v5.286 BUB1 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: BUB1.
Intellectual disability v5.286 BAP1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: BAP1.
Intellectual disability v5.286 ZNF292 Arina Puzriakova reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 ZMYND8 Arina Puzriakova reviewed gene: ZMYND8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 ZMYM3 Arina Puzriakova reviewed gene: ZMYM3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; 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 v5.286 WIPI2 Arina Puzriakova reviewed gene: WIPI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 UBAP2L Arina Puzriakova reviewed gene: UBAP2L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 TRA2B Arina Puzriakova reviewed gene: TRA2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 TMEM147 Arina Puzriakova reviewed gene: TMEM147: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 TCEAL1 Arina Puzriakova reviewed gene: TCEAL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; 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 v5.286 TAF4 Arina Puzriakova reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 TAF2 Arina Puzriakova reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 SUFU Arina Puzriakova commented on gene: SUFU: After NHS Genomic Medicine Service consideration, the rating of this gene has been updated to Green but the mode of inheritance has been set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal. Additional comments from reviewing GLHs: 'Consensus view: Monoallelic and biallelic'.
Intellectual disability v5.286 STXBP1 Arina Puzriakova reviewed gene: STXBP1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 SLC32A1 Arina Puzriakova reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 SHANK1 Arina Puzriakova reviewed gene: SHANK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 SEMA6B Arina Puzriakova reviewed gene: SEMA6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 SARS Arina Puzriakova commented on gene: SARS: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v5.286 ROR2 Arina Puzriakova edited their review of gene: ROR2: Added comment: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.; Changed rating: RED
Intellectual disability v5.286 ROBO1 Arina Puzriakova reviewed gene: ROBO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 RBSN Arina Puzriakova reviewed gene: RBSN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 PRKAR1B Arina Puzriakova reviewed gene: PRKAR1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 POU3F2 Arina Puzriakova reviewed gene: POU3F2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 PLXNA1 Arina Puzriakova reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 PLK1 Arina Puzriakova reviewed gene: PLK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 PAX6 Arina Puzriakova reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v5.286 PAN2 Arina Puzriakova reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 OTUD7A Arina Puzriakova reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 NUP214 Arina Puzriakova reviewed gene: NUP214: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 MTSS1L Arina Puzriakova commented on gene: MTSS1L: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v5.286 MED11 Arina Puzriakova reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 MAN2C1 Arina Puzriakova reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 LHX2 Arina Puzriakova reviewed gene: LHX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 KLHL20 Arina Puzriakova edited their review of gene: KLHL20: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 KIF4A Arina Puzriakova reviewed gene: KIF4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.286 KDM5A Arina Puzriakova reviewed gene: KDM5A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 KDM2B Arina Puzriakova reviewed gene: KDM2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 KCNK3 Arina Puzriakova edited their review of gene: KCNK3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v5.286 ITPR1 Arina Puzriakova edited their review of gene: ITPR1: Added comment: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 IQSEC2 Arina Puzriakova reviewed gene: IQSEC2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; 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 v5.286 INTS11 Arina Puzriakova edited their review of gene: INTS11: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 HUWE1 Arina Puzriakova reviewed gene: HUWE1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; 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 v5.286 HIST1H4E Arina Puzriakova reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 HECTD4 Arina Puzriakova reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 GRM7 Arina Puzriakova reviewed gene: GRM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 GRIA1 Arina Puzriakova edited their review of gene: GRIA1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 GCSH Arina Puzriakova reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 FRMD5 Arina Puzriakova commented on gene: FRMD5: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v5.286 FLNA Arina Puzriakova reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v5.286 FILIP1 Arina Puzriakova reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 ENTPD1 Arina Puzriakova edited their review of gene: ENTPD1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v5.286 DPH5 Arina Puzriakova reviewed gene: DPH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 DOHH Arina Puzriakova reviewed gene: DOHH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 DDX23 Arina Puzriakova reviewed gene: DDX23: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 CTR9 Arina Puzriakova reviewed gene: CTR9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 CPLX1 Arina Puzriakova reviewed gene: CPLX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 CLDN5 Arina Puzriakova reviewed gene: CLDN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 CCDC82 Arina Puzriakova reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 CAPRIN1 Arina Puzriakova reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 C2orf69 Arina Puzriakova edited their review of gene: C2orf69: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 BUB1 Arina Puzriakova edited their review of gene: BUB1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 BAP1 Arina Puzriakova reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 ZNF292 Arina Puzriakova Source NHS GMS was added to ZNF292.
Source Expert Review Green was added to ZNF292.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ZMYND8 Arina Puzriakova Source NHS GMS was added to ZMYND8.
Source Expert Review Green was added to ZMYND8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ZMYM3 Arina Puzriakova Source NHS GMS was added to ZMYM3.
Source Expert Review Green was added to ZMYM3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 WIPI2 Arina Puzriakova Source NHS GMS was added to WIPI2.
Source Expert Review Green was added to WIPI2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 UBAP2L Arina Puzriakova Source NHS GMS was added to UBAP2L.
Source Expert Review Green was added to UBAP2L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TRA2B Arina Puzriakova Source NHS GMS was added to TRA2B.
Source Expert Review Green was added to TRA2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TMEM147 Arina Puzriakova Source NHS GMS was added to TMEM147.
Source Expert Review Green was added to TMEM147.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TCEAL1 Arina Puzriakova Source NHS GMS was added to TCEAL1.
Source Expert Review Green was added to TCEAL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TAF4 Arina Puzriakova Source NHS GMS was added to TAF4.
Source Expert Review Green was added to TAF4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TAF2 Arina Puzriakova Source NHS GMS was added to TAF2.
Source Expert Review Green was added to TAF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 SUFU Arina Puzriakova Source NHS GMS was added to SUFU.
Source Expert Review Green was added to SUFU.
Mode of inheritance for gene SUFU was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 STXBP1 Arina Puzriakova Source NHS GMS was added to STXBP1.
Mode of inheritance for gene STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 SLC32A1 Arina Puzriakova Source NHS GMS was added to SLC32A1.
Source Expert Review Green was added to SLC32A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 SHANK1 Arina Puzriakova Source NHS GMS was added to SHANK1.
Source Expert Review Green was added to SHANK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 SEMA6B Arina Puzriakova Source NHS GMS was added to SEMA6B.
Source Expert Review Green was added to SEMA6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 SARS Arina Puzriakova Source NHS GMS was added to SARS.
Source Expert Review Green was added to SARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ROR2 Arina Puzriakova Source Expert Review Red was added to ROR2.
Source NHS GMS was added to ROR2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v5.286 ROBO1 Arina Puzriakova Source NHS GMS was added to ROBO1.
Source Expert Review Green was added to ROBO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 RBSN Arina Puzriakova Source NHS GMS was added to RBSN.
Source Expert Review Green was added to RBSN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PRKAR1B Arina Puzriakova Source NHS GMS was added to PRKAR1B.
Source Expert Review Green was added to PRKAR1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PPFIBP1 Arina Puzriakova Source NHS GMS was added to PPFIBP1.
Source Expert Review Green was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 POU3F2 Arina Puzriakova Source NHS GMS was added to POU3F2.
Source Expert Review Green was added to POU3F2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PLXNA1 Arina Puzriakova Source NHS GMS was added to PLXNA1.
Source Expert Review Green was added to PLXNA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PLK1 Arina Puzriakova Source NHS GMS was added to PLK1.
Source Expert Review Green was added to PLK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PAX6 Arina Puzriakova Source Expert Review Red was added to PAX6.
Source NHS GMS was added to PAX6.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v5.286 PAN2 Arina Puzriakova Source NHS GMS was added to PAN2.
Source Expert Review Green was added to PAN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 OTUD7A Arina Puzriakova Source NHS GMS was added to OTUD7A.
Source Expert Review Green was added to OTUD7A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 NUP214 Arina Puzriakova Source NHS GMS was added to NUP214.
Source Expert Review Green was added to NUP214.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 MTSS1L Arina Puzriakova Source NHS GMS was added to MTSS1L.
Source Expert Review Green was added to MTSS1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 MED11 Arina Puzriakova Source NHS GMS was added to MED11.
Source Expert Review Green was added to MED11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 MAN2C1 Arina Puzriakova Source NHS GMS was added to MAN2C1.
Source Expert Review Green was added to MAN2C1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 LHX2 Arina Puzriakova Source NHS GMS was added to LHX2.
Source Expert Review Green was added to LHX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KLHL20 Arina Puzriakova Source NHS GMS was added to KLHL20.
Source Expert Review Green was added to KLHL20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KIF4A Arina Puzriakova Source NHS GMS was added to KIF4A.
Source Expert Review Green was added to KIF4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KDM5A Arina Puzriakova Source NHS GMS was added to KDM5A.
Source Expert Review Green was added to KDM5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KDM2B Arina Puzriakova Source NHS GMS was added to KDM2B.
Source Expert Review Green was added to KDM2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KCNK3 Arina Puzriakova Source NHS GMS was added to KCNK3.
Source Expert Review Green was added to KCNK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ITPR1 Arina Puzriakova Source NHS GMS was added to ITPR1.
Mode of inheritance for gene ITPR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 IQSEC2 Arina Puzriakova Source NHS GMS was added to IQSEC2.
Mode of inheritance for gene IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.286 INTS11 Arina Puzriakova Source NHS GMS was added to INTS11.
Source Expert Review Green was added to INTS11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 HUWE1 Arina Puzriakova Source NHS GMS was added to HUWE1.
Mode of inheritance for gene HUWE1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.286 HIST1H4E Arina Puzriakova Source NHS GMS was added to HIST1H4E.
Source Expert Review Green was added to HIST1H4E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 HECTD4 Arina Puzriakova Source NHS GMS was added to HECTD4.
Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 GRM7 Arina Puzriakova Source NHS GMS was added to GRM7.
Source Expert Review Green was added to GRM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 GRIA1 Arina Puzriakova Source NHS GMS was added to GRIA1.
Source Expert Review Green was added to GRIA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 GCSH Arina Puzriakova Source NHS GMS was added to GCSH.
Source Expert Review Green was added to GCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 FRMD5 Arina Puzriakova Source NHS GMS was added to FRMD5.
Source Expert Review Green was added to FRMD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 FLNA Arina Puzriakova Source Expert Review Red was added to FLNA.
Source NHS GMS was added to FLNA.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v5.286 FILIP1 Arina Puzriakova Source NHS GMS was added to FILIP1.
Source Expert Review Green was added to FILIP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ENTPD1 Arina Puzriakova Source NHS GMS was added to ENTPD1.
Source Expert Review Green was added to ENTPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 DPH5 Arina Puzriakova Source NHS GMS was added to DPH5.
Source Expert Review Green was added to DPH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 DOHH Arina Puzriakova Source NHS GMS was added to DOHH.
Source Expert Review Green was added to DOHH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 DDX23 Arina Puzriakova Source NHS GMS was added to DDX23.
Source Expert Review Green was added to DDX23.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CTR9 Arina Puzriakova Source NHS GMS was added to CTR9.
Source Expert Review Green was added to CTR9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CPLX1 Arina Puzriakova Source NHS GMS was added to CPLX1.
Source Expert Review Green was added to CPLX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CLDN5 Arina Puzriakova Source NHS GMS was added to CLDN5.
Source Expert Review Green was added to CLDN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CCDC82 Arina Puzriakova Source NHS GMS was added to CCDC82.
Source Expert Review Green was added to CCDC82.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CAPRIN1 Arina Puzriakova Source NHS GMS was added to CAPRIN1.
Source Expert Review Green was added to CAPRIN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 C2orf69 Arina Puzriakova Source NHS GMS was added to C2orf69.
Source Expert Review Green was added to C2orf69.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 BUB1 Arina Puzriakova Source NHS GMS was added to BUB1.
Source Expert Review Green was added to BUB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 BAP1 Arina Puzriakova Source NHS GMS was added to BAP1.
Source Expert Review Green was added to BAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.285 HECTD4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.285 HECTD4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.285 SPATA5L1 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: SPATA5L1.
Intellectual disability v5.285 SPATA5 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: SPATA5.
Intellectual disability v5.285 RAB5C Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence for this gene to be promoted to green rating at the next GMS update.; to: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence (12 unrelated cases) for this gene to be promoted to green rating at the next GMS update.
Intellectual disability v5.285 RAB5C Achchuthan Shanmugasundram Classified gene: RAB5C as Amber List (moderate evidence)
Intellectual disability v5.285 RAB5C Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence for this gene to be promoted to green rating at the next GMS update.
Intellectual disability v5.285 RAB5C Achchuthan Shanmugasundram Gene: rab5c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.284 RAB5C Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: RAB5C.
Intellectual disability v5.284 ESAM Achchuthan Shanmugasundram changed review comment from: As reviewed by Julia Baptista, PMID:36996813 reported the identification of biallelic ESAM variants in 13 individuals from eight unrelated families, which included four foetuses. All nine born individuals had profound global developmental delay/ unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/ cerebral calcifications, the latter being also observed in the foetuses.

This gene has been associated with relevant phenotypes in OMIM (MIM #620371), but not yet in Gene2Phenotype.; to: As reviewed by Julia Baptista, PMID:36996813 reported the identification of biallelic ESAM variants in 13 individuals from eight unrelated families, which included four foetuses. All nine live-born individuals had profound global developmental delay/ unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/ cerebral calcifications, the latter being also observed in the foetuses.

This gene has been associated with relevant phenotypes in OMIM (MIM #620371), but not yet in Gene2Phenotype.
Intellectual disability v5.284 ESAM Achchuthan Shanmugasundram Classified gene: ESAM as Amber List (moderate evidence)
Intellectual disability v5.284 ESAM Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.284 ESAM Achchuthan Shanmugasundram Gene: esam has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.283 ESAM Achchuthan Shanmugasundram Phenotypes for gene: ESAM were changed from severe ID; seizures, spasticity to Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371
Intellectual disability v5.282 ESAM Achchuthan Shanmugasundram Publications for gene: ESAM were set to PMID: 36996813
Intellectual disability v5.281 ESAM Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: ESAM.
Tag Q3_23_NHS_review tag was added to gene: ESAM.
Intellectual disability v5.281 ESAM Achchuthan Shanmugasundram reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 36996813; Phenotypes: Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.280 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.279 PPP1R3F Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PPP1R3F.
Intellectual disability v5.279 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.280 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.280 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.280 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.279 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.278 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.279 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.278 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Intellectual disability v5.278 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Intellectual disability v5.278 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Intellectual disability v5.277 PPP1R3F Achchuthan Shanmugasundram reviewed gene: PPP1R3F: Rating: GREEN; Mode of pathogenicity: None; Publications: 37531237; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: NR2F2.
Tag Q3_23_NHS_review tag was added to gene: NR2F2.
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Classified gene: NR2F2 as Amber List (moderate evidence)
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Gene: nr2f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Classified gene: NR2F2 as Amber List (moderate evidence)
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Gene: nr2f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram changed review comment from: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901). This gene has been associated with these two phenotypes in both OMIM and Gene2Phenotype.

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.; to: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901). This gene has been associated with these two phenotypes in both OMIM and Gene2Phenotype. Some patients with CHD (MIM #615779) are reported with developmental delays in the OMIM record.

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram changed review comment from: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901).

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.; to: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901). This gene has been associated with these two phenotypes in both OMIM and Gene2Phenotype.

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram Publications for gene: NR2F2 were set to 29663647; 37500725
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram Publications for gene: NR2F2 were set to 29663647; 37500725
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram Publications for gene: NR2F2 were set to
Intellectual disability v5.275 NR2F2 Achchuthan Shanmugasundram Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.275 NR2F2 Achchuthan Shanmugasundram Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.275 NR2F2 Achchuthan Shanmugasundram Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.275 NR2F2 Achchuthan Shanmugasundram Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.274 NR2F2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.274 NR2F2 Achchuthan Shanmugasundram commented on gene: NR2F2: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901).

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.
Intellectual disability v5.274 NR2F2 Achchuthan Shanmugasundram reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29663647, 37500725; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: U2AF2.
Tag Q3_23_NHS_review tag was added to gene: U2AF2.
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from Developmental disorders to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.273 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.273 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.273 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 33057194
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram edited their review of gene: U2AF2: Changed publications to: 28135719, 31785789, 33057194, 34112922, 36747105, 37092751, 37134193
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Classified gene: U2AF2 as Amber List (moderate evidence)
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Celia Duff, there is sufficient evidence (>3 unrelated cases) available for the association of this gene with global developmental delay, intellectual disability and epilepsy. Hence, this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Classified gene: U2AF2 as Amber List (moderate evidence)
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Celia Duff, there is sufficient evidence (>3 unrelated cases) available for the association of this gene with global developmental delay, intellectual disability and epilepsy. Hence, this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Classified gene: U2AF2 as Amber List (moderate evidence)
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Celia Duff, there is sufficient evidence (>3 unrelated cases) available for the association of this gene with global developmental delay, intellectual disability and epilepsy. Hence, this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.271 U2AF2 Achchuthan Shanmugasundram reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28135719, 31785789, 34112922, 36747105, 37092751, 37134193; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.271 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ND4.
Intellectual disability v5.271 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ND1.
Intellectual disability v5.271 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ATP6.
Intellectual disability v5.271 PPP1R3F Zornitza Stark gene: PPP1R3F was added
gene: PPP1R3F was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PPP1R3F was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PPP1R3F were set to 37531237
Phenotypes for gene: PPP1R3F were set to Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Review for gene: PPP1R3F was set to GREEN
Added comment: 13 unrelated hemizygous individuals reported with functional evidence
Sources: Literature
Intellectual disability v5.271 RAB5C Zornitza Stark gene: RAB5C was added
gene: RAB5C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: RAB5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB5C were set to 37552066
Phenotypes for gene: RAB5C were set to Neurodevelopmental disorder MONDO:0700092, RAB5C-related
Review for gene: RAB5C was set to GREEN
Added comment: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All have mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Intellectual disability v5.271 NR2F2 Katherine Lachlan reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37500725; Phenotypes: intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, vascular malformations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.271 ATM Zornitza Stark reviewed gene: ATM: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ataxia-telangiectasia, MIM#208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.271 ESAM Julia Baptista gene: ESAM was added
gene: ESAM was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review
Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESAM were set to PMID: 36996813
Phenotypes for gene: ESAM were set to severe ID; seizures, spasticity
Review for gene: ESAM was set to GREEN
Added comment: Lecca et al 2023 reported thirteen patients from eight unrelated families with biallelic loss of function variants (nonsense, frameshift, canonical splice site, all predicted to result in a transcript targeted for nonsense-mediated decay). Protein staining assays in one of the brain fetal samples confirmed loss the loss of protein.
The phenotype reported in this cohort is of a severe neurodevelopmental disorder with brain anomalies (calcifications, hydrocephalus, enlarged ventricles, cerebral atrophy, etc), and dysmorphic features.
Sources: Literature, Expert Review
Intellectual disability v5.271 TP63 Arina Puzriakova Phenotypes for gene: TP63 were changed from Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome; 3, 604292; Split-hand/foot malformation 4, 605289; Hay-Wells syndrome, 106260; ADULT syndrome, 103285; Limb-mammary syndrome, 603543; Rapp-Hodgkin syndrome, 129400; Orofacial cleft 8, 129400 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 v5.270 ERMARD Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted from amber to red.
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted from amber to red.
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted from amber to red.
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted to red.
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted to red.
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.268 U2AF2 Celia Duff-Farrier changed review comment from: Literature evidence Ref1-5, identification of affected patients in the diagnostic setting (CVA database, 19:55661148:C>T ) and further accounts in open access databases (ClinVar and LOVD), make this gene suitable for clinical review and upgrading to a green gene status on relevant panels. It is associated with a phenotype encompassing dysmorphism, epilepsy, developmental delay, intellectual disability, and brain malformation Ref1-5. There is a recent publication that proposes an extension of this phenotype to include hypomyelination leukodystrophy Ref6. A loss of function mechanism has been suggested, associated with disruption of RNA recognition motifs required for the function of U2AF2 as a pre-mRNA splicing factor Ref4. At least one recurrent pathogenic variant has been identified by this review U2AF2 c.445C>T p.(Arg149Trp). U2AF2 is constrained for missense in gnomAD Z=4.71.
total variants reported
1) De novo U2AF2 (NM_007279.3:c.445C>T p.(Arg149Trp)) recurrent variant; 1x patient in Hiraide (PubMed: 34112922), 1x patient in Kittock (PubMed: 37092751), 2x patients in Kaplanis (Pubmed: 33057194), 7x patients in the Leiden Open Variation Database (LOVD, https://www.lovd.nl/), 1x patient in house BGL and 4x additional on CVA
2) De novo U2AF2 c.603G>T; 1 patient in Wang 2023 (PubMed: 36747105)
3) De novo U2AF2 c.470C>T p.Pro157Leu) in Kuroda (PubMed: 37134193)
4) 9x additional pathogenic or likely pathogenic variants on LOVD
5) 2x additional likely pathogenic variants on ClinVar

References
1.       PubMed: 28135719 McRae (2017)-DDD data
2.       PubMed: 31785789 Turner (2019)-DDD data
3.       PubMed: 34112922 Hiraide (2021) de novo U2AF2 c.445C>T p.R149W
4.       PubMed: 36747105 Wang (2023) de novo U2AF2 c.603G>T, p.163_201del
5.       PubMed: 37092751 Kittock (2023) de novo U2AF2 c.445C>T p.R149W
Possible emerging phenotype of hypomyelinating leukodystrophy
6.       PubMed: 37134193 Kuroda (2023); to: Literature evidence Ref1-5, identification of affected patients in the diagnostic setting (CVA database, 19:55661148:C>T ) and further accounts in open access databases (ClinVar and LOVD), make this gene suitable for clinical review and upgrading to a green gene status on relevant panels. It is associated with a phenotype encompassing dysmorphism, epilepsy, developmental delay, intellectual disability, and brain malformation Ref1-5. There is a recent publication that proposes an extension of this phenotype to include hypomyelination leukodystrophy Ref6. A loss of function mechanism has been suggested, associated with disruption of RNA recognition motifs required for the function of U2AF2 as a pre-mRNA splicing factor Ref4. At least one recurrent pathogenic variant has been identified by this review U2AF2 c.445C>T p.(Arg149Trp). U2AF2 is constrained for missense in gnomAD Z=4.71.
total variants/patients identified
1) De novo U2AF2 (NM_007279.3:c.445C>T p.(Arg149Trp)) recurrent variant; 1x patient in Hiraide (PubMed: 34112922), 1x patient in Kittock (PubMed: 37092751), 2x patients in Kaplanis (Pubmed: 33057194), 7x patients in the Leiden Open Variation Database (LOVD, https://www.lovd.nl/), 1x patient in house BGL and 4x additional on CVA
2) De novo U2AF2 c.603G>T; 1 patient in Wang 2023 (PubMed: 36747105)
3) De novo U2AF2 c.470C>T p.Pro157Leu) in Kuroda (PubMed: 37134193)
4) 9x additional pathogenic or likely pathogenic variants on LOVD
5) 2x additional likely pathogenic variants on ClinVar
6) We are collaborating with a researcher in the USA with a cohort of 40+ cases.


References
1.       PubMed: 28135719 McRae (2017)-DDD data
2.       PubMed: 31785789 Turner (2019)-DDD data
3.       PubMed: 34112922 Hiraide (2021) de novo U2AF2 c.445C>T p.R149W
4.       PubMed: 36747105 Wang (2023) de novo U2AF2 c.603G>T, p.163_201del
5.       PubMed: 37092751 Kittock (2023) de novo U2AF2 c.445C>T p.R149W
Possible emerging phenotype of hypomyelinating leukodystrophy
6.       PubMed: 37134193 Kuroda (2023)
Intellectual disability v5.268 U2AF2 Celia Duff-Farrier reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 28135719):(PMID: 31785789):(PMID: 34112922):(PMID: 36747105):(PMID: 37092751):(PMID 37134193); Phenotypes: intellectual disability, global developmental delay, dysmorphism, epilepsy, brain malformation, microcephaly, possible emerging phenotype of hypomyelinating leukodystrophy.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Classified gene: NEUROG1 as Amber List (moderate evidence)
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases reported with global developmental delay/ intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Gene: neurog1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Classified gene: NEUROG1 as Amber List (moderate evidence)
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases reported with global developmental delay/ intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Gene: neurog1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Classified gene: NEUROG1 as Amber List (moderate evidence)
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases reported with global developmental delay/ intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Gene: neurog1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: NEUROG1.
Tag Q3_23_NHS_review tag was added to gene: NEUROG1.
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 36647078; 33439489; 23419067; 26077850
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.265 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.265 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from developmental delay; behavioural problems; cranial dysinnervation; absent corneal reflex to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.264 NEUROG1 Achchuthan Shanmugasundram reviewed gene: NEUROG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23419067, 26077850, 33439489, 36647078; Phenotypes: Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.264 CMIP Sarah Leigh reviewed gene: CMIP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.264 CMIP Sarah Leigh Classified gene: CMIP as Red List (low evidence)
Intellectual disability v5.264 CMIP Sarah Leigh Gene: cmip has been classified as Red List (Low Evidence).
Intellectual disability v5.263 UQCRB Arina Puzriakova Phenotypes for gene: UQCRB were changed from Mitochondrial complex III deficiency, nuclear type 3, 615158 to Mitochondrial complex III deficiency, nuclear type 3, OMIM:615158
Intellectual disability v5.262 CMIP Sarah Leigh Publications for gene: CMIP were set to PMID: 22689534; 28504353
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Classified gene: ATP6V0C as Amber List (moderate evidence)
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Classified gene: ATP6V0C as Amber List (moderate evidence)
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Classified gene: ATP6V0C as Amber List (moderate evidence)
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Tag watchlist was removed from gene: ATP6V0C.
Tag Q3_23_promote_green tag was added to gene: ATP6V0C.
Tag Q3_23_NHS_review tag was added to gene: ATP6V0C.
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33090716; 33190975; 36074901; 37161035
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33090716; 33190975; 36074901; 37161035
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33090716; 33190975; 36074901; 37161035
Intellectual disability v5.259 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33090716; 33190975; 36074901; 37161035
Intellectual disability v5.259 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33190975; 33090716; 36074901; 37161035
Intellectual disability v5.258 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33190975; 33090716; 36074901; 37161035
Intellectual disability v5.258 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 33190975; 33090716
Intellectual disability v5.257 ATP6V0C Achchuthan Shanmugasundram edited their review of gene: ATP6V0C: Changed publications to: 24623842, 33190975, 36074901, 37161035
Intellectual disability v5.257 ATP6V0C Achchuthan Shanmugasundram changed review comment from: 17 of 32 total patients had impaired intellectual development.; to: PMID:36074901 - 16 of 27 patients identified with monoallelic ATP6V0C variants, including a patient each from PMID:24623842 and PMID:33190975 had impaired intellectual development, while 21 patients had developmental delay.

PMID:37161035 - One of three patients identified with monoallelic ATP6V0C variant had impaired intellectual development and language delay, while another had developmental delay and speech delay.

This gene has been associated with relevant phenotypes in OMIM (MIM #620465) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.257 ATP6V0C Achchuthan Shanmugasundram edited their review of gene: ATP6V0C: Changed publications to: 24623842, 33190975, 35600075, 36074901, 37161035
Intellectual disability v5.257 ATP6V0C Achchuthan Shanmugasundram reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: None; Publications: 33190975, 35600075, 36074901, 37161035; Phenotypes: Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.257 PTCH1 Arina Puzriakova Phenotypes for gene: PTCH1 were changed from Basal cell nevus syndrome, 109400Basal cell carcinoma, somatic, 605462Holoprosencephaly-7, 610828; HOLOPROSENCEPHALY-7 to Holoprosencephaly 7, OMIM:610828
Intellectual disability v5.256 NEUROG1 Julia Baptista gene: NEUROG1 was added
gene: NEUROG1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: NEUROG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG1 were set to 36647078; 33439489; 23419067; 26077850
Phenotypes for gene: NEUROG1 were set to developmental delay; behavioural problems; cranial dysinnervation; absent corneal reflex
Review for gene: NEUROG1 was set to GREEN
Added comment: Five affected individuals from four independently reported families (Middle Eastern, Portuguese, Indian and Turkish backgrounds) with biallelic microdeletion, missense, nonsense or frameshift variants.

Affected individuals present at birth or in early infancy with corneal opacities due to absent blinking, sensorineural deafness associated with hypoplastic or malformed cochlea and hypoplasia or agenesis of CN VIII was reported. Developmental delay, poor speech, autistic behavior and dysmorphic facial features were also present.
Sources: Literature
Intellectual disability v5.256 ATP6V0C Julia Baptista reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: None; Publications: 36074901; Phenotypes: Epilepsy, Intellectual Disability, Microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.256 DNAH14 Sarah Leigh Publications for gene: DNAH14 were set to 35438214
Intellectual disability v5.256 DNAH14 Sarah Leigh Classified gene: DNAH14 as Red List (low evidence)
Intellectual disability v5.256 DNAH14 Sarah Leigh Gene: dnah14 has been classified as Red List (Low Evidence).
Intellectual disability v5.255 DNAH14 Sarah Leigh reviewed gene: DNAH14: Rating: RED; Mode of pathogenicity: None; Publications: 26036949, 30125339, 26636390, 32848021; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.255 FAM111A Tracy Lester reviewed gene: FAM111A: Rating: RED; Mode of pathogenicity: None; Publications: 23684011, 37023242; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.255 CMIP Tord Jonson edited their review of gene: CMIP: Changed phenotypes to: HP:0012759 Neurodevelopmental abnormality, HP:0000717 Autism, HP:0007018 Attention deficit hyperactivity disorder, HP:0001250 Seizure, HP:0011471 Gastrostomy tube feeding in infancy
Intellectual disability v5.255 CMIP Tord Jonson changed review comment from: CMIP (MANE Select NM_198390) loss of function-variants (deletions) have been reported in two studies that describes patients with syndromic ASD and co-morbid gastrointestinal issues. See Van der Aa et al., 2012, Haploinsufficiency of CMIP in a girl with autism spectrum disorder and developmental delay due to a de novo deletion on chromosome 16q23.2 (PMID: 22689534); and Luo et al., 2017, CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues (PMID: 28504353). In addition, we have observed a local case with a de novo deletion encompassing only the genes CMIP and GAN in a patient with gastrostomy, intellectual disability, autism, ADHD and seizures.
Sources: Other; to: CMIP (MANE Select NM_198390) loss of function-variants (deletions) have been reported in two studies that describes patients with syndromic ASD and co-morbid gastrointestinal issues. See Van der Aa et al., 2012, Haploinsufficiency of CMIP in a girl with autism spectrum disorder and developmental delay due to a de novo deletion on chromosome 16q23.2 (PMID: 22689534); and Luo et al., 2017, CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues (PMID: 28504353). In addition, we have observed a local case with a de novo deletion encompassing only the genes CMIP and GAN in a patient with gastrostomy, intellectual disability, autism, ADHD and seizures.
Intellectual disability v5.255 CMIP Tord Jonson gene: CMIP was added
gene: CMIP was added to Intellectual disability - microarray and sequencing. Sources: Other
Mode of inheritance for gene: CMIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CMIP were set to PMID: 22689534; 28504353
Phenotypes for gene: CMIP were set to HP:0012759; HP:0000717; HP:0007018; HP:0001250; HP:0011471
Penetrance for gene: CMIP were set to unknown
Review for gene: CMIP was set to GREEN
gene: CMIP was marked as current diagnostic
Added comment: CMIP (MANE Select NM_198390) loss of function-variants (deletions) have been reported in two studies that describes patients with syndromic ASD and co-morbid gastrointestinal issues. See Van der Aa et al., 2012, Haploinsufficiency of CMIP in a girl with autism spectrum disorder and developmental delay due to a de novo deletion on chromosome 16q23.2 (PMID: 22689534); and Luo et al., 2017, CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues (PMID: 28504353). In addition, we have observed a local case with a de novo deletion encompassing only the genes CMIP and GAN in a patient with gastrostomy, intellectual disability, autism, ADHD and seizures.
Sources: Other
Intellectual disability v5.255 PABPC1 Sarah Leigh Tag Q3_23_phenotype tag was added to gene: PABPC1.
Intellectual disability v5.255 PABPC1 Sarah Leigh edited their review of gene: PABPC1: Added comment: PABPC1 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 35511136 reports four de novo PABPC1 variants in four unrelated cases with a phenotype of global DD, movement coordination disorders,
seizures, behavioral disorders and mild facial dysmorphisms. Intellectual disability ranged in the cases from profound (1/4), IQ: 61 (1/4) and IQ: 79 (2/4). Seizures were apparent in the all of the three cases where it was assessed.
Molecular modeling of the variants suggested that they would result in a reduced binding affinity to the messenger RNA metabolism-related protein - PAIP2. This predicted effect was seen in coimmunoprecipitation assays between variant PABPC1 and PAIP2 (PMID: 35511136). Further functional studies in PMID: 35511136, showed that the proliferation of neural progenitor cells in Pabpc1 knockdown mouse embryo brains were decreased, this effect was rescued by the wild-type Pabpc1, but not by the variants c.1691A>G (p.Glu564Gly) or c.1709T>C (p.Ile570Thr).
Other variants were identified in 3/4 cases in PMID: 35511136, two of these had a ACMG VUS classification (RBBP4: c.845A>G, p.(Asn282Ser), IGF2R: c.1850G>A p.Cys617Tyr), while the third variant was monoallelic, whereas bialleic variants in this gene are associated with disease (KDM5B: c.2265dupA, p.(Tyr755*))(PMID: 35511136, table 1).; Changed rating: GREEN
Intellectual disability v5.255 PABPC1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: PABPC1.
Tag Q3_23_MOI tag was added to gene: PABPC1.
Intellectual disability v5.255 PABPC1 Sarah Leigh Classified gene: PABPC1 as Amber List (moderate evidence)
Intellectual disability v5.255 PABPC1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.255 PABPC1 Sarah Leigh Gene: pabpc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.254 CLCNKA Sarah Leigh Phenotypes for gene: CLCNKA were changed from Bartter syndrome, type 4b, digenic, 613090; Infantile Bartter syndrome with sensorineural deafness, intellectual disability to Bartter syndrome, type 4b, digenic, OMIM:613090; Bartter disease type 4B, MONDO:0000909
Intellectual disability v5.253 CLCNKA Sarah Leigh Publications for gene: CLCNKA were set to
Intellectual disability v5.253 CLCNKA Sarah Leigh Added comment: Comment on mode of inheritance: Digenic CLCNKA & CLCNKB variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090)(PMID: 15044642;18310267;32488762). The current GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.
Intellectual disability v5.253 CLCNKA Sarah Leigh Mode of inheritance for gene: CLCNKA was changed from to Other
Intellectual disability v5.252 CLCNKB Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for CLCNKB should be BIALLELIC, autosomal or pseudoautosomal. Although digenic CLCNKB & CLCNKA variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090), the current GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.
Intellectual disability v5.252 CLCNKB Sarah Leigh Mode of inheritance for gene: CLCNKB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.251 CLCNKB Sarah Leigh Tag digenic was removed from gene: CLCNKB.
Tag monogenic-polygenic tag was added to gene: CLCNKB.
Intellectual disability v5.251 MKL2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.251 MKL2 Achchuthan Shanmugasundram Classified gene: MKL2 as Amber List (moderate evidence)
Intellectual disability v5.251 MKL2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As there are only two unrelated cases reported so far, this gene should be rated amber for now.
Intellectual disability v5.251 MKL2 Achchuthan Shanmugasundram Gene: mkl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.250 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.250 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.250 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.249 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.249 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental phenotype with dysmorphic features to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.249 MKL2 Achchuthan Shanmugasundram Publications for gene: MKL2 were set to 37013900
Intellectual disability v5.249 MKL2 Achchuthan Shanmugasundram Publications for gene: MKL2 were set to 37013900
Intellectual disability v5.248 MKL2 Achchuthan Shanmugasundram Publications for gene: MKL2 were set to 37013900
Intellectual disability v5.248 MKL2 Achchuthan Shanmugasundram Publications for gene: MKL2 were set to PMID:37013900
Intellectual disability v5.247 MKL2 Achchuthan Shanmugasundram commented on gene: MKL2: PMID:37013900 - Two unrelated paediatric cases with de novo variants in MKL2 gene (p.Arg103Gly & p.Ala91Pro) were reported with mild dysmorphic features, severe intellectual disability, global developmental delays, speech apraxia, and impulse control issues. Functional studies in a Drosophila model suggest a gain of function disease mechanism.
Intellectual disability v5.247 MKL2 Achchuthan Shanmugasundram reviewed gene: MKL2: 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: 37013900; Phenotypes: neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.247 ATG4D Achchuthan Shanmugasundram Classified gene: ATG4D as Amber List (moderate evidence)
Intellectual disability v5.247 ATG4D Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases with mild cognitive impairment and hence this gene should be rated amber with the current evidence.
Intellectual disability v5.247 ATG4D Achchuthan Shanmugasundram Gene: atg4d has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.246 ATG4D Achchuthan Shanmugasundram changed review comment from: PMID:36765070 - Three individuals from two different families were reported with a neurodevelopmental disorder and identified with compound heterozygous variants in ATG4D gene (family 1: :c.266G>A/ p.Ser89Asn & c.839A>G/ p.Tyr280Cys; family 2: c.1310_1328del/ p.Asp437Alafs*37 & c.1066G>A/ p.Asp356Asn). Patient from family 1 and one of two patients from family 2 had mild cognitive impairment.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'limited' rating in the DD panel), but not yet in OMIM.; to: PMID:36765070 - Three individuals from two different families were reported with a neurodevelopmental disorder and identified with compound heterozygous variants in ATG4D gene (family 1: :c.266G>A/ p.Ser89Asn & c.839A>G/ p.Tyr280Cys; family 2: c.1310_1328del/ p.Asp437Alafs*37 & c.1066G>A/ p.Asp356Asn). Patient from family 1 and one of two patients from family 2 had mild cognitive impairment. Based on the clinical, bioinformatic, and functional data, the authors also concluded that bi-allelic loss-of-function variants in ATG4D contribute to the pathogenesis of syndromic neurodevelopmental disorder.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'limited' rating in the DD panel), but not yet in OMIM.
Intellectual disability v5.246 ATG4D Achchuthan Shanmugasundram changed review comment from: PMID:36765070 - Three individuals from two different families were reported with a neurodevelopmental disorder and identified with compound heterozygous variants in ATG4D gene (family 1: :c.266G>A/ p.Ser89Asn & c.839A>G/ p.Tyr280Cys; family 2: c.1310_1328del/ p.Asp437Alafs*37 & c.1066G>A/ p.Asp356Asn). Patient from family 1 and one of two patients from family 2 had cognitive impairment.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'limited' rating in the DD panel), but not yet in OMIM.; to: PMID:36765070 - Three individuals from two different families were reported with a neurodevelopmental disorder and identified with compound heterozygous variants in ATG4D gene (family 1: :c.266G>A/ p.Ser89Asn & c.839A>G/ p.Tyr280Cys; family 2: c.1310_1328del/ p.Asp437Alafs*37 & c.1066G>A/ p.Asp356Asn). Patient from family 1 and one of two patients from family 2 had mild cognitive impairment.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'limited' rating in the DD panel), but not yet in OMIM.
Intellectual disability v5.246 ATG4D Achchuthan Shanmugasundram Phenotypes for gene: ATG4D were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.246 ATG4D Achchuthan Shanmugasundram Phenotypes for gene: ATG4D were changed from neurodevelopmental disorder characterized by speech and motor impairment to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.245 ATG4D Achchuthan Shanmugasundram edited their review of gene: ATG4D: Changed rating: AMBER; Changed publications to: 36765070; Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.245 AKT3 Arina Puzriakova Phenotypes for gene: AKT3 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, 603387; HEMIMEGALENCEPHALY AKT3 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, OMIM:615937
Intellectual disability v5.244 ATG4D Achchuthan Shanmugasundram commented on gene: ATG4D
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PSMC3.
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from neurodevelopmental delay to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.240 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.240 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to PMID: 37256937
Intellectual disability v5.239 PSMC3 Achchuthan Shanmugasundram reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32500975, 37256937; Phenotypes: ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Classified gene: KCNH5 as Amber List (moderate evidence)
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence for the association of this gene to intellectual disability. Hence, this gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Gene: kcnh5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Classified gene: KCNH5 as Amber List (moderate evidence)
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence for the association of this gene to intellectual disability. Hence, this gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Gene: kcnh5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Classified gene: KCNH5 as Amber List (moderate evidence)
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence for the association of this gene to intellectual disability. Hence, this gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Gene: kcnh5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from INFANTILE EPILEPTIC ENCEPHALOPATHY to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Mode of pathogenicity for gene: KCNH5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Mode of pathogenicity for gene: KCNH5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Mode of pathogenicity for gene: KCNH5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.237 KCNH5 Achchuthan Shanmugasundram Mode of pathogenicity for gene: KCNH5 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 v5.236 KCNH5 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNH5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.236 KCNH5 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNH5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.235 KCNH5 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: KCNH5.
Intellectual disability v5.235 KCNH5 Achchuthan Shanmugasundram reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23647072, 35874597, 36307226, 24133262; Phenotypes: developmental and epileptic encephalopathy, MONDO:0100062, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.235 CLCNKB Sarah Leigh Tag polygenic was removed from gene: CLCNKB.
Tag digenic tag was added to gene: CLCNKB.
Intellectual disability v5.235 CLCNKB Sarah Leigh Phenotypes for gene: CLCNKB were changed from Bartter syndrome, type 3, 607364Bartter syndrome, type 4b, digenic, 613090; BARTTER SYNDROME TYPE 4B to Bartter syndrome, type 3, OMIM:607364; Bartter disease type 3, MONDO:0011822; Bartter syndrome, type 4b, digenic, OMIM:613090; Bartter disease type 4B, MONDO:0000909
Intellectual disability v5.234 LETM1 Sarah Leigh changed review comment from: LETM1 variants has been associated with Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 and as moderate Gen2Phen gene for LETM1-related neurodevelopmental disorder.
PMID: 36055214 reports 10 LETM1 variants in 18 patients from 11 unrelated families with childhood-onset neurodegeneration with multisystem involvement, many of whom were gathered using the GeneMatcher Program. The most common clinical features of this cohort, where an assessment could be made, were: mitochondrial respiratory complex deficiencies 11/11 (100%), global developmental delay / intellectual disability 17/18 (94%), bilateral sensorineural hearing loss 11/14 (78%) , impaired vision 10/10 (100%), cerebellar ataxia 7/9 (78%), seizures 10/15 (67%), hypotonia 11/18 (61%) (PMID: 36055214, figure 1c).; to: LETM1 variants have been associated with Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 and as moderate Gen2Phen gene for LETM1-related neurodevelopmental disorder.
PMID: 36055214 reports 10 LETM1 variants in 18 patients from 11 unrelated families with childhood-onset neurodegeneration with multisystem involvement, many of whom were gathered using the GeneMatcher Program. The most common clinical features of this cohort, where an assessment could be made, were: mitochondrial respiratory complex deficiencies 11/11 (100%), global developmental delay / intellectual disability 17/18 (94%), bilateral sensorineural hearing loss 11/14 (78%) , impaired vision 10/10 (100%), cerebellar ataxia 7/9 (78%), seizures 10/15 (67%), hypotonia 11/18 (61%) (PMID: 36055214, figure 1c).
Intellectual disability v5.234 SLC22A5 Sarah Leigh Mode of inheritance for gene: SLC22A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.233 SLC22A5 Sarah Leigh changed review comment from: Comment on mode of inheritance: The mode of inheritance for SLC22A5 variants should be BOTH Monoallelic and Biallelic. Although, most of the evidence for symptoms associated SLC22A5 are seen in a patients with biallelic variants (HGNC:10969, OMIM:603377, Gen2Phen, Orphanet:118781, ClinGen), a few individuals heterozygous for SLC22A5 variants have been seen with a milder phenotype (PMID: 10545605; 11261427).; to: Comment on mode of inheritance: The mode of inheritance for SLC22A5 variants should be BIALLELIC, autosomal or pseudoautosomal. Although, heterozygous SLC22A5 variants have been seen in a few cases, these are detectable biochemically and are not associated with clear clinical presentation (PMID: 10545605; 11261427).
Intellectual disability v5.233 RPS6KA3 Arina Puzriakova Tag Q3_23_MOI tag was added to gene: RPS6KA3.
Intellectual disability v5.233 RPS6KA3 Arina Puzriakova Publications for gene: RPS6KA3 were set to
Intellectual disability v5.232 RPS6KA3 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from XLR to XLD (monoallelic variants in females may cause disease) at the next GMS panel update as several affected female carriers have been reported. ID in female carriers can range from mild to severe which is within the scope of the panel (PMIDs: 12210291; 12030896; 12558110; 17318637). This would also match the current MOI on other GMS panels and OMIM.
Intellectual disability v5.232 RPS6KA3 Arina Puzriakova Mode of inheritance for gene: RPS6KA3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.231 RPS6KA3 Arina Puzriakova Phenotypes for gene: RPS6KA3 were changed from Coffin-Lowry syndrome, 303600Mental retardation, X-linked 19, 300844; COFFIN-LOWRY SYNDROME (CLS) to Coffin-Lowry syndrome, OMIM:303600; Intellectual developmental disorder, X-linked 19, OMIM:300844
Intellectual disability v5.230 KCNH5 Dmitrijs Rots reviewed gene: KCNH5: 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: PMID: 36307226, 35874597; Phenotypes: Neurodevelopmental disorder and Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.230 LETM1 Sarah Leigh Entity copied from Ataxia and cerebellar anomalies - narrow panel v4.27
Intellectual disability v5.230 LETM1 Sarah Leigh gene: LETM1 was added
gene: LETM1 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review Amber,Expert Review
Q3_23_promote_green, Q3_23_MOI tags were added to gene: LETM1.
Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LETM1 were set to 36055214; 33815143
Phenotypes for gene: LETM1 were set to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Intellectual disability v5.229 SLC25A24 Sarah Leigh Publications for gene: SLC25A24 were set to
Intellectual disability v5.228 SLC25A24 Sarah Leigh Phenotypes for gene: SLC25A24 were changed from to Fontaine progeroid syndrome, OMIM; 612289; Fontaine progeroid syndrome, MONDO:0012853
Intellectual disability v5.227 SLC22A5 Sarah Leigh Publications for gene: SLC22A5 were set to 9916797; 10425211; 15714519; 10480371; 9700603; 2235122; 20027113; 9634512; 11058897; 3974805; 10051646
Intellectual disability v5.227 SLC22A5 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for SLC22A5 variants should be BOTH Monoallelic and Biallelic. Although, most of the evidence for symptoms associated SLC22A5 are seen in a patients with biallelic variants (HGNC:10969, OMIM:603377, Gen2Phen, Orphanet:118781, ClinGen), a few individuals heterozygous for SLC22A5 variants have been seen with a milder phenotype (PMID: 10545605; 11261427).
Intellectual disability v5.227 SLC22A5 Sarah Leigh Mode of inheritance for gene: SLC22A5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.226 SLC22A5 Sarah Leigh Phenotypes for gene: SLC22A5 were changed from Carnitine deficiency, systemic primary, 212140 to Carnitine deficiency, systemic primary, OMIM:212140; systemic primary carnitine deficiency disease, MONDO:0008919
Intellectual disability v5.225 AGTPBP1 Achchuthan Shanmugasundram Classified gene: AGTPBP1 as Amber List (moderate evidence)
Intellectual disability v5.225 AGTPBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating at the next major update.
Intellectual disability v5.225 AGTPBP1 Achchuthan Shanmugasundram Gene: agtpbp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.224 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: AGTPBP1.
Intellectual disability v5.224 AGTPBP1 Achchuthan Shanmugasundram changed review comment from: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe in several patients: Two had severe cognitive delay, one had profound cognitive delay, five had no speech and four had no visual recognition. In addition, functional studies with mouse models have recapitulated the human phenotype.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature; to: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe in several patients: Two had severe cognitive delay, one had profound cognitive delay, five had no speech and four had no visual recognition. In addition, functional studies with mouse models have recapitulated the human phenotype.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature
Intellectual disability v5.224 AGTPBP1 Achchuthan Shanmugasundram changed review comment from: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe, and several patients were unable to speak or have eye contact.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature; to: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe in several patients: Two had severe cognitive delay, one had profound cognitive delay, five had no speech and four had no visual recognition. In addition, functional studies with mouse models have recapitulated the human phenotype.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature
Intellectual disability v5.224 AGTPBP1 Achchuthan Shanmugasundram gene: AGTPBP1 was added
gene: AGTPBP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
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 Neurodegeneration, childhood-onset, with cerebellar atrophy, OMIM:618276
Review for gene: AGTPBP1 was set to GREEN
Added comment: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe, and several patients were unable to speak or have eye contact.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature
Intellectual disability v5.223 ZNF292 Achchuthan Shanmugasundram reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 64, OMIM:619188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Classified gene: PIP5K1C as Amber List (moderate evidence)
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (nine unrelated cases and supporting functional evidence) for promoting this gene to green rating in the next GMS review.
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.222 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PIP5K1C.
Intellectual disability v5.222 PIP5K1C Achchuthan Shanmugasundram gene: PIP5K1C was added
gene: PIP5K1C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIP5K1C were set to 37451268
Phenotypes for gene: PIP5K1C were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: PIP5K1C was set to GREEN
Added comment: Three de novo heterozygous missense variants in PIP5K1C (p.Glu146Lys, p.Tyr205Cys & p.Tyr221Cys) were identified in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. Intellectual disability was reported in all nine children and seizures were present in seven children, of which three had developmental and epileptic encephalopathy. In addition, there is functional evidence available, which includes an in vivo zebrafish model that recapitulates the human phenotype (developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities) (PMID:37451268).

This gene has been associated with another phenotype (Lethal congenital contractural syndrome 3, MIM #611369) in both OMIM and Gene2Phenotype, but not yet associated with this neurodevelopmental disorders in either databases.
Sources: Literature
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Classified gene: TMEM63B as Amber List (moderate evidence)
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) in support of promoting this gene to green rating in the next GMS review.
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Gene: tmem63b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.220 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: TMEM63B.
Intellectual disability v5.220 TMEM63B Achchuthan Shanmugasundram gene: TMEM63B was added
gene: TMEM63B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63B were set to 37421948
Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: TMEM63B was set to GREEN
Added comment: PMID:37421948 - 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment.
Sources: Literature
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Classified gene: DHX9 as Amber List (moderate evidence)
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated cases) in support of promoting this gene to green rating at the next GMS review.
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Gene: dhx9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Classified gene: DHX9 as Amber List (moderate evidence)
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated cases) in support of promoting this gene to green rating at the next GMS review.
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Gene: dhx9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.218 DHX9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DHX9.
Intellectual disability v5.218 DHX9 Achchuthan Shanmugasundram gene: DHX9 was added
gene: DHX9 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX9 were set to 37467750
Phenotypes for gene: DHX9 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: DHX9 was set to GREEN
Added comment: PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder (NDD) and three were reported with Charcot-Marie-Tooth disease (CMT). All 14 cases with NDD had developmental delay, of which eight were reported with intellectual disability (4 severe, 1 moderate, 3 mild). Two cases did not have ID, one had borderline ID and three cases were too young (0-5 years old).
Sources: Literature
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: CNOT9.
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Classified gene: CNOT9 as Amber List (moderate evidence)
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (seven unrelated cases) for this gene to be promoted to Green at the next major update.
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Gene: cnot9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.216 CNOT9 Achchuthan Shanmugasundram gene: CNOT9 was added
gene: CNOT9 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CNOT9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT9 were set to 37092538
Phenotypes for gene: CNOT9 were set to intellectual disability, MONDO:0001071
Review for gene: CNOT9 was set to GREEN
Added comment: PMID:37092538 - Seven unrelated individuals with de novo variants in CNOT9 gene (one individual each with variants p.Arg46Gly, p.Pro131Leu and p.Arg227His and four individuals with p.Arg292Trp) were reported with a neurodevelopmental disorder. All affected persons have intellectual disability (three severe, three mild and one unclassified) and five of them have seizures.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.; to: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.; to: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.214 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.214 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: SLC30A9.
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from ?Birk-Landau-Perez syndrome 617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.212 SLC30A9 Achchuthan Shanmugasundram Publications for gene: SLC30A9 were set to 28334855
Intellectual disability v5.211 SLC30A9 Achchuthan Shanmugasundram reviewed gene: SLC30A9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28334855, 34716203, 37041080; Phenotypes: Birk-Landau-Perez syndrome, OMIM:617595; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram edited their review of gene: DAGLA: 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 v5.209 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DAGLA.
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from developmental delay; ataxia; complex oculomotor abnormality to intellectual disability, MONDO:0001071
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.206 DAGLA Achchuthan Shanmugasundram Publications for gene: DAGLA were set to 35737950
Intellectual disability v5.206 DAGLA Achchuthan Shanmugasundram Publications for gene: DAGLA were set to PMID: 35737950
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 35737950; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.205 BUB1 Arina Puzriakova Phenotypes for gene: BUB1 were changed from Congenital microcephaly; Global developmental delay; Intellectual disability; Abnormal heart morphology; Growth delay to Microcephaly 30, primary, autosomal recessive, OMIM:620183
Intellectual disability v5.204 BUB1 Arina Puzriakova commented on gene: BUB1
Intellectual disability v5.204 BUB1 Arina Puzriakova Tag Q4_22_MOI was removed from gene: BUB1.
Intellectual disability v5.204 DAGLA Irina Ziravecka gene: DAGLA was added
gene: DAGLA was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to PMID: 35737950
Phenotypes for gene: DAGLA were set to developmental delay; ataxia; complex oculomotor abnormality
Mode of pathogenicity for gene: DAGLA was set to Other
Review for gene: DAGLA was set to GREEN
Added comment: PMID: 35737950 - nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype.
Sources: Literature
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.202 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.202 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability; Parkinsonism to Intellectual disability, MONDO:0001071
Intellectual disability v5.200 PTPA Achchuthan Shanmugasundram reviewed gene: PTPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36073231; Phenotypes: Intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.; to: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay supported by functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.197 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.197 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Postnatal microcephaly, progressive brain atrophy and global developmental delay to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.196 FOXR1 Achchuthan Shanmugasundram edited their review of gene: FOXR1: Changed phenotypes to: Global developmental delay, HP:0001263, microcephaly, MONDO:0001149, Brain atrophy, HP:0012444
Intellectual disability v5.196 FOXR1 Achchuthan Shanmugasundram reviewed gene: FOXR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34723967; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.196 KDM6B Sarah Leigh Phenotypes for gene: KDM6B were changed from Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, 618505 to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, OMIM:618505; neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MONDO:0032790
Intellectual disability v5.195 KDM6B Sarah Leigh Publications for gene: KDM6B were set to 21937992; 31124279
Intellectual disability v5.194 DALRD3 Arina Puzriakova Classified gene: DALRD3 as Amber List (moderate evidence)
Intellectual disability v5.194 DALRD3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Konstantinos Varvagiannis. Rating Amber as this is a good candidate gene but only a single family has been reported to date with variants. Additional evidence needed prior to adding the gene as diagnostic-grade.
Intellectual disability v5.194 DALRD3 Arina Puzriakova Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.193 SMCHD1 Arina Puzriakova Mode of inheritance for gene: SMCHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.191 PSMC3 Dmitrijs Rots gene: PSMC3 was added
gene: PSMC3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to PMID: 37256937
Phenotypes for gene: PSMC3 were set to neurodevelopmental delay
Mode of pathogenicity for gene: PSMC3 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: PSMC3 was set to GREEN
Added comment: 23 individuals with NDD due to 15 different de novo missense variants in PMID: 37256937.
Sources: Literature
Intellectual disability v5.191 MKL2 Dmitrijs Rots gene: MKL2 was added
gene: MKL2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: MKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MKL2 were set to PMID:37013900
Phenotypes for gene: MKL2 were set to neurodevelopmental phenotype with dysmorphic features
Mode of pathogenicity for gene: MKL2 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: MKL2 was set to GREEN
Added comment: 2 cases with de novo missense GoF variants in MRTFB (previously known as MKL2) + functional evidence
Sources: Literature
Intellectual disability v5.191 EIF4A2 Sarah Leigh Classified gene: EIF4A2 as Amber List (moderate evidence)
Intellectual disability v5.191 EIF4A2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rating Green at the major review.
Intellectual disability v5.191 EIF4A2 Sarah Leigh Gene: eif4a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.190 EIF4A2 Sarah Leigh gene: EIF4A2 was added
gene: EIF4A2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q3_23_promote_green tags were added to gene: EIF4A2.
Mode of inheritance for gene: EIF4A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EIF4A2 were set to 36528028
Phenotypes for gene: EIF4A2 were set to Neurodevelopmental disorder
Review for gene: EIF4A2 was set to GREEN
Added comment: EIF4A2 has not been associated with a phenotype in OMIM, Gen2Phen or Mondo at the time of reporting. PMID: 36528028 reports the findings of an international collaboration through Matchmaker Exchange, where EIF4A2 variants are found in cases with neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy. A total of 15 EIF4A2 variants have been reported in PMID: 36528028, with 12 variants occurring as de novo monoallelic in 12 individuals and 3 as biallelic in two unrelated cases (one as homozygote and the other as compound heterozygous). Severe intellectual was seen in 6/10 unrelated cases where an assessment was made, epilepsy was evident in 10/14 unrelated cases and 13/14 cases had hyptonia. Functional studies were also presented and it would appear that both loss and gain functions maybe associated with EIF4A2 variants.
Sources: Literature
Intellectual disability v5.189 TTI1 Sarah Leigh Classified gene: TTI1 as Amber List (moderate evidence)
Intellectual disability v5.189 TTI1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.189 TTI1 Sarah Leigh Gene: tti1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.188 TTI1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TTI1.
Intellectual disability v5.188 TTI1 Sarah Leigh gene: TTI1 was added
gene: TTI1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TTI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTI1 were set to 36724785
Phenotypes for gene: TTI1 were set to neurodevelopmental disorder with microcephaly
Review for gene: TTI1 was set to GREEN
Added comment: TTI1 has not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. At least 2 variants have been reported. PMID: 36724785 reported 15 TTI1 variants as either homozygotes (2 families) or compound heterozygotes (7 families) in cases with a neurodevelopmental disorder with microcephaly. In all cases the parents were heterozygous carriers of the TTI1 variant identified in the affected child. Development delay was observed in all of the families (9/9), moderate to severe intellectual disability was evident in all families where it could be assessed (8/8) and severe microcephaly was present in members of 5/9 families. Supportive functional results were also presented.
Sources: Literature
Intellectual disability v5.187 TSPOAP1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TSPOAP1.
Intellectual disability v5.187 TSPOAP1 Sarah Leigh Entity copied from Childhood onset dystonia, chorea or related movement disorder v3.13
Intellectual disability v5.187 TSPOAP1 Sarah Leigh gene: TSPOAP1 was added
gene: TSPOAP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSPOAP1 were set to 33539324
Phenotypes for gene: TSPOAP1 were set to Dystonia, intellectual disability and cerebellar atrophy
Intellectual disability v5.186 SRRM2 Sarah Leigh Added comment: Comment on publications: www.hindawi.com/journals/humu/2023/6633248
Intellectual disability v5.186 SRRM2 Sarah Leigh Publications for gene: SRRM2 were set to 35567594; 33057194
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Classified gene: GRM7 as Amber List (moderate evidence)
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (six unrelated cases and supporting mouse model) for this gene to be promoted to GREEN rating at the next GMS review.
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Gene: grm7 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 32248644; 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram edited their review of gene: GRM7: Changed publications to: 32248644, 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 32248644; 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 2248644; 32286009
Intellectual disability v5.183 GRM7 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: GRM7.
Intellectual disability v5.183 GRM7 Achchuthan Shanmugasundram gene: GRM7 was added
gene: GRM7 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 2248644; 32286009
Phenotypes for gene: GRM7 were set to Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities, OMIM:618922
Review for gene: GRM7 was set to GREEN
Added comment: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising severe to profound global developmental delays, intellectual disability, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).
Sources: Literature
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, there is more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.; to: As reviewed by Konstantinos Varvagiannis, there are more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CCDC82.
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Classified gene: CCDC82 as Amber List (moderate evidence)
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Gene: ccdc82 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Classified gene: CCDC82 as Amber List (moderate evidence)
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Gene: ccdc82 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from Global developmental delay; Intellectual disability; Spastic paraparesis to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.180 CCDC82 Achchuthan Shanmugasundram commented on gene: CCDC82: As reviewed by Konstantinos Varvagiannis, there is more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.
Intellectual disability v5.180 CCDC82 Achchuthan Shanmugasundram reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: None; Publications: 27457812, 28397838, 35118659, 35373332; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.180 FLNA Sarah Leigh edited their review of gene: FLNA: Changed rating: RED
Intellectual disability v5.180 FLNA Sarah Leigh reviewed gene: FLNA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.180 FLNA Sarah Leigh Tag Q2_23_demote_red tag was added to gene: FLNA.
Intellectual disability v5.180 FLNA Sarah Leigh Publications for gene: FLNA were set to
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: UBE3C.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Classified gene: UBE3C as Amber List (moderate evidence)
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases associating biallelic variants in UBE3C gene with intellectual disability. Hence, this gene should be rated AMBER.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Gene: ube3c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Classified gene: UBE3C as Amber List (moderate evidence)
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases associating biallelic variants in UBE3C gene with intellectual disability. Hence, this gene should be rated AMBER.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Gene: ube3c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.178 UBE3C Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: UBE3C.
Intellectual disability v5.178 UBE3C Achchuthan Shanmugasundram gene: UBE3C was added
gene: UBE3C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: UBE3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE3C were set to 36401616
Phenotypes for gene: UBE3C were set to Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities, OMIM:620270
Review for gene: UBE3C was set to AMBER
Added comment: PMID:36401616 reported three patients from two unrelated families with homozygous variants in UBE3C gene and presenting with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. All three patients had severe intellectual disability. The RNA studies in some patients with LoF variants provided evidence for the LoF effect.
Sources: Literature
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: HECTD4.
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.175 HECTD4 Achchuthan Shanmugasundram gene: HECTD4 was added
gene: HECTD4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HECTD4 were set to 36401616
Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, OMIM:620250
Review for gene: HECTD4 was set to GREEN
Added comment: PMID:36401616 reported seven patients from five unrelated families with either homozygous (3 families) or compound heterozygous variants (2 families) in HECTD4 gene and presenting with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. All seven patients had severe (4 cases) or moderate (3 cases) intellectual disability.
Sources: Literature
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TRA2B.
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram edited their review of gene: TRA2B: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram changed review comment from: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature; to: PMID:36549593 reported 12 individuals from 11 unrelated families identified with 11 different heterozygous variants in TRA2B gene. The variants arose de novo in 10 families, while the variant was inherited from father to son in one family. 6 variants were expected to disrupt the translation start site in exon 1 (start-loss variants), 3 were expected to disrupt the splicing process at the exon 2/3 boundary (splice-affecting variants), and the remaining 2 were expected to produce a premature stop codon (truncating variants).

These patients presented with a neurodevelopmental disorder comprising developmental delay/ intellectual disability (in all patients), axial or global hypotonia (10 patients), delayed motor milestones (all patients), behavioural issues (8 patients), speech impairment (9 patients), epilepsy (7 patients, initial presentation as infantile spasms in 6 and unclassified epileptic encephalopathy in 1), brain abnormalities (10 patients) and microcephaly (5 patients). The degree of ID was severe to profound for 6 individuals, moderate to severe for 2 and mild to moderate for 3.

In addition, functional studies in mice showed that heterozygous knockout mice developed normal, while complete knockout mice cannot develop embryonically.

This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram gene: TRA2B was added
gene: TRA2B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TRA2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRA2B were set to 36549593
Phenotypes for gene: TRA2B were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: TRA2B was set to GREEN
Added comment: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 ATG4D Dmitrijs Rots gene: ATG4D was added
gene: ATG4D was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ATG4D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG4D were set to 36765070
Phenotypes for gene: ATG4D were set to neurodevelopmental disorder characterized by speech and motor impairment
Review for gene: ATG4D was set to GREEN
Added comment: Morimoto et al., described 3 cases from 2 families with ATG4D biallelic variants and provided some functional evidence.
No data about homozygous or compound heterozygous with two rare variants in ATG4D in gnomAD database.
Sources: Literature
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CLDN5.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.167 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from epilepsy, MONDO:0005027 to intellectual disability, MONDO:0001071
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram edited their review of gene: CLDN5: Changed phenotypes to: intellectual disability, MONDO:0001071
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram changed review comment from: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature; to: PMID:36477332 reported the identification of de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a number of clinical features including developmental delay including intellectual disability, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognisable pattern of pontine atrophy and brain calcifications. All seven living patients over four years of age were reported to have intellectual disability.

In addition, functional studies from zebrafish model also provided parallel evidence that CLDN5 variants cause a neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.

This gene has been associated with relevant phenotypes in Gene2Phenotype (CLDN5-related neurodevelopmental disorder with 'limited' rating in the DD panel), but not in OMIM.
Sources: Literature
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram edited their review of gene: CLDN5: Changed phenotypes to: intellectual disability, MONDO:0001071tual
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram gene: CLDN5 was added
gene: CLDN5 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 36477332
Phenotypes for gene: CLDN5 were set to epilepsy, MONDO:0005027
Review for gene: CLDN5 was set to GREEN
Added comment: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TCEAL1.
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram changed review comment from: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behavior, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature; to: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behaviour, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram gene: TCEAL1 was added
gene: TCEAL1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TCEAL1 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: TCEAL1 were set to 36368327
Phenotypes for gene: TCEAL1 were set to Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, OMIM:301094
Review for gene: TCEAL1 was set to GREEN
Added comment: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behavior, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability reported (one in literature and another from Diagnostic Discovery initiative).; to: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability (one in literature and another from Diagnostic Discovery initiative).
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Classified gene: FEM1C as Amber List (moderate evidence)
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability reported (one in literature and another from Diagnostic Discovery initiative).
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Gene: fem1c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram changed review comment from: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram changed review comment from: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature; to: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram edited their review of gene: FEM1C: Changed rating: AMBER
Intellectual disability v5.161 POU3F2 Sarah Leigh Classified gene: POU3F2 as Amber List (moderate evidence)
Intellectual disability v5.161 POU3F2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.161 POU3F2 Sarah Leigh Gene: pou3f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.161 POU3F2 Sarah Leigh Classified gene: POU3F2 as Amber List (moderate evidence)
Intellectual disability v5.161 POU3F2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.161 POU3F2 Sarah Leigh Gene: pou3f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.160 POU3F2 Sarah Leigh gene: POU3F2 was added
gene: POU3F2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: POU3F2.
Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POU3F2 were set to 37207645
Phenotypes for gene: POU3F2 were set to neurodevelopmental delay with hyperphagic obesity
Review for gene: POU3F2 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37207645 reports eight POU3F2 variants in the unrelated cases of neurodevelopmental delay with hyperphagic obesity, with no other variants detected in other candidate genes. Intellectual disability was apparent in 6/7 of these cases from infancy to early childhood. The remaining variant : NM_005604.4 c.135C>A, p.Tyr45* was found in a mother and son, where the son was classified as having intellectual disability, the mother did not. Excluding the mother and son, all of the remaining cases carrying POU3F2 variants had neurodevelopmental delay.
Sources: Literature
Intellectual disability v5.159 ETFB Sarah Leigh Publications for gene: ETFB were set to 30847515; 11980892; 25778941; 24360804; 27021474; 28489334; 30089828; 36495139
Intellectual disability v5.158 ETFB Sarah Leigh Publications for gene: ETFB were set to 0
Intellectual disability v5.157 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from GLUTARIC ACIDURIA TYPE 2B to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Intellectual disability v5.156 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from GLUTARIC ACIDURIA TYPE 2A to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Intellectual disability v5.155 NUP214 Eleanor Williams Tag Q2_23_promote_green tag was added to gene: NUP214.
Intellectual disability v5.155 NUP214 Eleanor Williams commented on gene: NUP214: After consultation with the Genomics England clinical team it has been decided that there is just enough evidence to promote this gene to green as there are 4 unrelated families and developmental delay is reported in all.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FILIP1.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram changed review comment from: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.153 FILIP1 Achchuthan Shanmugasundram changed review comment from: Sources: Literature; to: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.153 FILIP1 Achchuthan Shanmugasundram gene: FILIP1 was added
gene: FILIP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36344539; 37163662
Phenotypes for gene: FILIP1 were set to intellectual disability, MONDO:0001071
Review for gene: FILIP1 was set to GREEN
Added comment: Sources: Literature
Intellectual disability v5.152 FLNA Tracy Lester reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: None; Publications: 20301392; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.; to: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN rating at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Classified gene: TAF4 as Amber List (moderate evidence)
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Gene: taf4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Classified gene: TAF4 as Amber List (moderate evidence)
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Gene: taf4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.151 INTS11 Arina Puzriakova Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Complex neurodevelopmental disorder, MONDO:0100038
Intellectual disability v5.150 INTS11 Arina Puzriakova commented on gene: INTS11
Intellectual disability v5.150 TAF4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TAF4.
Intellectual disability v5.150 PRKACB Arina Puzriakova Phenotypes for gene: PRKACB were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, OMIM:619143
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from Developmental disorder to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 33875846; 28191890; 27026076
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.145 TAF4 Achchuthan Shanmugasundram reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28191890, 33875846, 35904126; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ZMYND8.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.143 ZMYND8 Achchuthan Shanmugasundram edited their review of gene: ZMYND8: Added comment: As reviewed by Konstantinos Varvagiannis, PMID:35916866 reported intellectual disability in10 out of 11 unrelated cases, of which one patient had profound ID and two had moderate ID.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype (with 'moderate' rating in the DD panel).; Changed phenotypes to: intellectual disability, MONDO:0001071
Intellectual disability v5.143 ZMYND8 Achchuthan Shanmugasundram reviewed gene: ZMYND8: Rating: GREEN; Mode of pathogenicity: None; Publications: 32530565, 35916866; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.143 ZMYND15 Achchuthan Shanmugasundram Publications for gene: ZMYND15 were set to 35916866; 32530565
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.143 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram commented on gene: ZMYND15
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.137 ZMYND15 Achchuthan Shanmugasundram Tag curated_removed tag was added to gene: ZMYND15.
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: Comment on gene classification - This gene should remain as Green rating as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: Comment on gene classification - This gene should remain as Green as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: Comment on gene classification - This gene should remain as Green rating as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram reviewed gene: PRSS12: Rating: GREEN; Mode of pathogenicity: None; Publications: 12459588, 25529582; Phenotypes: Intellectual developmental disorder, autosomal recessive 1, OMIM:249500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: MAN2C1.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.; to: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Abnormality of the corpus callosum; Ventriculomegaly; Polymicrogyria; Abnormality of the face; Macrocephaly to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.135 MAN2C1 Achchuthan Shanmugasundram commented on gene: MAN2C1: As reviewed by Konstantinos Varvagiannis, there are three unrelated cases reported with intellectual disability in PMID:35045343.

In addition, this gene has been associated with relevant phenotypes in both OMIM (MIM #619775) and Gene2Phenotype (with 'strong' rating in DD panel).
Intellectual disability v5.135 MAN2C1 Achchuthan Shanmugasundram reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35045343; Phenotypes: Congenital disorder of deglycosylation 2, OMIM:619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram changed review comment from: As reviewed already, there are two cases reported in PMIDs: 25885783 & 34645488. Additional cases were reported in PMIDs: 20655035 & 23352160, however without much clinical details. Hence, the rating should remain amber.; to: As reviewed already, there are two cases reported in PMIDs: 25885783 & 34645488. Additional cases were reported in PMIDs: 20655035 & 23352160, however without much clinical details. Hence, the rating should remain amber.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.132 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.131 FAAH2 Achchuthan Shanmugasundram reviewed gene: FAAH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25885783, 34645488; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.131 ITPR1 Arina Puzriakova Phenotypes for gene: ITPR1 were changed from Gillespie syndrome 206700 to Gillespie syndrome, OMIM:206700; Spinocerebellar ataxia 15, OMIM:606658; Spinocerebellar ataxia 29, congenital nonprogressive, OMIM:117360
Intellectual disability v5.130 ITPR1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update inline with the review by Tracy Lester. Although not observed in all, some patients do exhibit cognitive deficits which may be an early and severe feature. There are sufficient unrelated cases with heterozygous variants and ID (associated with either Gillespie or SCA) to warrant including this MOI on this panel.
Intellectual disability v5.130 ITPR1 Arina Puzriakova Mode of inheritance for gene: ITPR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.129 ITPR1 Arina Puzriakova Publications for gene: ITPR1 were set to 22986007
Intellectual disability v5.128 ITPR1 Arina Puzriakova Tag Q2_23_MOI tag was added to gene: ITPR1.
Tag Q2_23_NHS_review tag was added to gene: ITPR1.
Intellectual disability v5.128 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, 210900; BLOOM SYNDROME to Bloom syndrome, OMIM:210900
Intellectual disability v5.128 BLM Arina Puzriakova Publications for gene: BLM were set to
Intellectual disability v5.127 BLM Arina Puzriakova reviewed gene: BLM: Rating: ; Mode of pathogenicity: None; Publications: 22514588, 23552953, 36646944; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram reviewed gene: NSF: Rating: RED; Mode of pathogenicity: None; Publications: 36645181; Phenotypes: Developmental and epileptic encephalopathy 96, OMIM:619340; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram Publications for gene: NSF were set to 31675180; 36645181
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram Publications for gene: NSF were set to 31675180
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.123 ENTPD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ENTPD1.
Intellectual disability v5.123 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with biallelic variants in ENTPD1 and with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

PMID:35758610 reported two siblings with biallelic variants in ENTPD1. The proband was mildly intellectually disabled and her brother was moderately clinically disabled based on clinical observations.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.123 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290; Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Intellectual disability v5.122 ENTPD1 Achchuthan Shanmugasundram edited their review of gene: ENTPD1: Changed publications to: 35471564, 35758610
Intellectual disability v5.122 COASY Sarah Leigh Publications for gene: COASY were set to 24360804
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to Green rating at the next major update.
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been includes as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals. Hence, this gene can be promoted to Green in the next major update.; to: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been includes as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals. Hence, this gene can be promoted to Green in the next major update.
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.118 ENTPD1 Achchuthan Shanmugasundram reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35471564; Phenotypes: Spastic paraplegia 64, autosomal recessive, OMIM:615683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.118 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6, 615643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290
Intellectual disability v5.117 SUFU Arina Puzriakova Tag Q4_22_expert_review tag was added to gene: SUFU.
Intellectual disability v5.117 RNF13 Arina Puzriakova Phenotypes for gene: RNF13 were changed from Cortical visual impairment; Epileptic encephalopathy, early infantile, 73, 618379; Failure to thrive; Seizures; Congenital microcephaly; Abnormal muscle tone; Feeding difficulties; Intellectual disability; Global developmental delay; Sensorineural hearing impairment to Developmental and epileptic encephalopathy 73, OMIM:618379
Intellectual disability v5.116 CHMP3 Arina Puzriakova Classified gene: CHMP3 as Red List (low evidence)
Intellectual disability v5.116 CHMP3 Arina Puzriakova Added comment: Comment on list classification: Rating Red for now as only a single case has been reported to date.
Intellectual disability v5.116 CHMP3 Arina Puzriakova Gene: chmp3 has been classified as Red List (Low Evidence).
Intellectual disability v5.115 CHMP3 Arina Puzriakova gene: CHMP3 was added
gene: CHMP3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to 35710109
Phenotypes for gene: CHMP3 were set to Complex spastic quadriplegia associated with developmental delay and seizures
Added comment: Cohen-Barak et al., 2022 (PMID: 35710109) reported on a consanguineous family, in which five individuals presented with intellectual and progressive motor disabilities, seizures and spastic quadriplegia, associated with a homozygous variant in CHMP3. Patient derived fibroblasts expressed ultrastructural and molecular features of impaired autophagy, partially rescued by ectopic expression of WT-CHMP3.
Sources: Literature
Intellectual disability v5.114 RAC3 Arina Puzriakova Publications for gene: RAC3 were set to 29276006; 30293988
Intellectual disability v5.113 RAC3 Arina Puzriakova Classified gene: RAC3 as Green List (high evidence)
Intellectual disability v5.113 RAC3 Arina Puzriakova Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability v5.112 RAC3 Arina Puzriakova All sources for gene: RAC3 were removed
Intellectual disability v5.112 RAC3 Arina Puzriakova All sources for gene: RAC3 were removed
Intellectual disability v5.111 GRIN2B Arina Puzriakova Publications for gene: GRIN2B were set to
Intellectual disability v5.110 GRIN2B Arina Puzriakova Phenotypes for gene: GRIN2B were changed from Mental Retardation, Dominant; Mental retardation, autosomal dominant 6, 613970; AUTISM to Intellectual developmental disorder, autosomal dominant 6, with or without seizures, OMIM:613970; Developmental and epileptic encephalopathy 27, OMIM:616139
Intellectual disability v5.109 LHX2 Sarah Leigh Classified gene: LHX2 as Amber List (moderate evidence)
Intellectual disability v5.109 LHX2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.109 LHX2 Sarah Leigh Gene: lhx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.108 LHX2 Sarah Leigh gene: LHX2 was added
gene: LHX2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: LHX2.
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LHX2 were set to 37057675
Phenotypes for gene: LHX2 were set to neurodevelopmental disorder
Review for gene: LHX2 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37057675 reports 17 predominanly de novo LHX2 variants in a panel of patients with a variable neurodevelopmental disorder. Haploinsufficiency and functional studies are supportive of a loss-of-function pathogenic action of the reported LHX2 variants.
Sources: Literature
Intellectual disability v5.107 ITPR1 Tracy Lester edited their review of gene: ITPR1: Added comment: PMID:29925855 - All 7 EOA patients with ITPR1 de novo variants (3 from cohort #1; 4 from cohort #2) presented with infantile onset cerebellar ataxia starting before the age of 2 years, including delayed motor milestones (Table 2). Cognitive deficits of variable degree were observed in 3 out of 4 patients where this information was available, reaching from only mild dyscalculia (P2) to severe intellectual disability with a speech vocabulary of only a few words (P7 at age 12 years). In contrast, patient P1 showed normal intelligence with an IQ of 97.

PMID:27108797 - Here, we report that both recessive and dominant ITPR1 mutations cause Gillespie syndrome. ITPR1 is a predominant isoform in the brain among the three types of ITPRs and is strongly expressed in cerebellar Purkinje cells.31 Mice with complete homozygosity for Itpr1 ablation suffer from severe epilepsy and ataxia and die either in utero or before weaning.32 Consistently, ITPR1 mutations have been reported to cause cerebellar diseases including late-onset spinocerebellar ataxia type 15 (SCA15 [MIM: 606658]),33 congenital nonprogressive spinocerebellar ataxia and mild cognitive impairment (SCA29 [MIM: 117360]),34 infantile-onset cerebellar ataxia with mild cognitive deficit,35 and childhood-onset ataxic cerebellar palsy with moderate intellectual disability36 (see ITPR1 schematic diagram in Figure 3A).
Affected individuals had similar iris anomalies and neonatal ataxia with progressive cerebellar atrophy (Figure 2). Moderate to severe intellectual disabilities were noted in the three individuals with recessive mutations (F1:II1, F2:II1, and F3:II1; Table 1). In contrast, the affected individual F4:II1 aged 18 years and harboring the de novo c.7687_7689del mutation was reported to have normal intelligence (Table 1).

As de novo variants are associated with ID/DD the inheritance should be updated to be BOTH AD and AR.; Set current diagnostic: yes
Intellectual disability v5.107 ITPR1 Tracy Lester reviewed gene: ITPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29925855, 27108797; Phenotypes: developmental delay, intellectual disability, hypotonia, ataxia, cerebellar malformatons; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SLC32A1.
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram changed review comment from: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.
Sources: Literature; to: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.

Although this gene has not yet been associated with phenotypes in OMIM, it has been added to Gene2Phenotype with 'moderate' rating in the DD panel.

Sources: Literature
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram gene: SLC32A1 was added
gene: SLC32A1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SLC32A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC32A1 were set to 36073542
Phenotypes for gene: SLC32A1 were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: SLC32A1 was set to GREEN
Added comment: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.
Sources: Literature
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from to Intellectual disability, MONDO:0001071
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 CSTF2 Achchuthan Shanmugasundram reviewed gene: CSTF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 32816001; Phenotypes: Intellectual disability, MONDO:0001071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.98 HIST1H4E Ronnie Wright reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v5.98 SRRM2 Alistair Pagnamenta reviewed gene: SRRM2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35567594, 33057194; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PRKAR1B.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.93 PRKAR1B Achchuthan Shanmugasundram reviewed gene: PRKAR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33833410; Phenotypes: Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 (16 individuals from 12 families) shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).; to: As reviewed by Konstantinos Varvagiannis, all individuals (16 individuals from 12 families) reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).; to: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 (16 individuals from 12 families) shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PPFIBP1.
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of brain morphology; Abnormality of the cerebral white matter; Cerebral calcification; Abnormal cortical gyration; Hypertonia; Spastic tetraplegia; Generalized hypotonia; Small for gestational age; Growth delay; Failure to thrive; Feeding difficulties; abnormal heart morphology; Hearing abnormality; Cryptorchidism; Abnormality of vision to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).; to: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram edited their review of gene: PPFIBP1: Changed phenotypes to: Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35830857; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.90 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.90 KDM2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.90 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: KDM2B.
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Publications for gene: KDM2B were set to 36322151
Intellectual disability v5.87 KDM2B Achchuthan Shanmugasundram Publications for gene: KDM2B were set to PMID: 36322151; 35128353; 35710456
Intellectual disability v5.86 KDM2B Achchuthan Shanmugasundram reviewed gene: KDM2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 36322151; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.87 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.87 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.87 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194; 33874999
Intellectual disability v5.86 HNRNPD Achchuthan Shanmugasundram Publications for gene: HNRNPD were set to 33057194
Intellectual disability v5.85 HNRNPD Achchuthan Shanmugasundram Tag watchlist tag was added to gene: HNRNPD.
Intellectual disability v5.85 HNRNPD Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), several additional individuals with neurodevelopmental disorders carrying de novo HNRNPD variants identified in an international cohort have been reported in PMID:33874999. These probands displayed a high prevalence of DD/ID, speech delay, and ASD and/or other behavioural phenotypes. As this is a large cohort study and there is no complete information about DD/ID phenotypes in these probands, this gene should remain as AMBER.; to: As reviewed by Zornitza Stark (Australian Genomics), several additional individuals with neurodevelopmental disorders carrying de novo HNRNPD variants identified in an international cohort have been reported in PMID:33874999. These probands displayed a high prevalence of DD/ID, speech delay, and ASD and/or other behavioural phenotypes. As this is a large cohort study and there is no complete information about DD/ID phenotypes in these probands, this gene should remain as AMBER.

The 'watchlist' tag has been added to review this rating in light of new evidence in the future.
Intellectual disability v5.85 HNRNPD Achchuthan Shanmugasundram reviewed gene: HNRNPD: Rating: AMBER; Mode of pathogenicity: None; Publications: 33874999; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.85 WIPI2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there are three unrelated families with homozygous variants in WIPI2 gene presenting with varying degrees of intellectual disability supported by functional evidence. Hence, this gene can be promoted to GREEN at the next major review.; to: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there are three unrelated families with homozygous variants in WIPI2 gene presenting with varying degrees of intellectual disability (moderate to profound) and supported by functional evidence. Hence, this gene can be promoted to GREEN at the next major review.
Intellectual disability v5.85 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: WIPI2.
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111; 34557665
Intellectual disability v5.84 WIPI2 Achchuthan Shanmugasundram Publications for gene: WIPI2 were set to 30968111
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Amber List (moderate evidence)
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Amber List (moderate evidence)
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Amber List (moderate evidence)
Intellectual disability v5.83 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.82 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Amber List (moderate evidence)
Intellectual disability v5.82 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.81 WIPI2 Achchuthan Shanmugasundram Classified gene: WIPI2 as Red List (low evidence)
Intellectual disability v5.81 WIPI2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there are three unrelated families with homozygous variants in WIPI2 gene presenting with varying degrees of intellectual disability supported by functional evidence. Hence, this gene can be promoted to GREEN at the next major review.
Intellectual disability v5.81 WIPI2 Achchuthan Shanmugasundram Gene: wipi2 has been classified as Red List (Low Evidence).
Intellectual disability v5.80 WIPI2 Achchuthan Shanmugasundram reviewed gene: WIPI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30968111, 34557665; Phenotypes: ?Intellectual developmental disorder with short stature and variable skeletal anomalies, OMIM:618453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PLXNA1.
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Classified gene: PLXNA1 as Amber List (moderate evidence)
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for this gene to be promoted to GREEN at the next major review. The MOI can also be set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are more than three cases each with both monoallelic and biallelic variants.
Intellectual disability v5.80 PLXNA1 Achchuthan Shanmugasundram Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.79 PLXNA1 Achchuthan Shanmugasundram Classified gene: PLXNA1 as Amber List (moderate evidence)
Intellectual disability v5.79 PLXNA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for this gene to be promoted to GREEN at the next major review. The MOI can also be set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are more than three cases each with both monoallelic and biallelic variants.
Intellectual disability v5.79 PLXNA1 Achchuthan Shanmugasundram Gene: plxna1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.78 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.77 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.77 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062 to Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.77 PLXNA1 Achchuthan Shanmugasundram Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Neurodevelopmental disorder with cerebral and eye anomalies; Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955; developmental and epileptic encephalopathy, MONDO:0100062
Intellectual disability v5.76 PLXNA1 Achchuthan Shanmugasundram Publications for gene: PLXNA1 were set to 28464511; 34054129; 34415653
Intellectual disability v5.76 PLXNA1 Achchuthan Shanmugasundram Publications for gene: PLXNA1 were set to 34054129
Intellectual disability v5.75 PLXNA1 Achchuthan Shanmugasundram Deleted their review
Intellectual disability v5.75 PLXNA1 Achchuthan Shanmugasundram reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28464511, 34054129, 34415653; Phenotypes: Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955, developmental and epileptic encephalopathy, MONDO:0100062; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.75 PLXNA1 Achchuthan Shanmugasundram reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28464511, 34054129, 34415653; Phenotypes: Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955, developmental and epileptic encephalopathy, MONDO:0100062; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: KIF4A.
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.75 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Publications for gene: KIF4A were set to 24812067; 34346154
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from ?Intellectual developmental disorder, X-linked 100, OMIM:300923 to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Phenotypes for gene: KIF4A were changed from INTELLECTUAL DISABILITY to ?Intellectual developmental disorder, X-linked 100, OMIM:300923
Intellectual disability v5.74 KIF4A Achchuthan Shanmugasundram Publications for gene: KIF4A were set to 24812067; 34346154
Intellectual disability v5.73 KIF4A Achchuthan Shanmugasundram Publications for gene: KIF4A were set to 24812067; 34346154
Intellectual disability v5.73 KIF4A Achchuthan Shanmugasundram Publications for gene: KIF4A were set to 24812067
Intellectual disability v5.72 KIF4A Achchuthan Shanmugasundram Classified gene: KIF4A as Amber List (moderate evidence)
Intellectual disability v5.72 KIF4A Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there are at least four unrelated cases with hemizygous variants in KIF4A gene and presenting with intellectual disability. This evidence is sufficient for promoting to GREEN rating at the next major review.
Intellectual disability v5.72 KIF4A Achchuthan Shanmugasundram Gene: kif4a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.71 KIF4A Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), there are at least four unrelated cases with hemizygous variants in KIF4A gene and presenting with intellectual disability.

PMID:24812067 reported a family in which five males spanning three generations had intellectual disability, speech delay and global developmental delay and four of these males developed seizures in late childhood–adolescence.

PMID:34346154 reported 11 unrelated cases expanding the phenotypic spectrum to include developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of clinical manifestations. Of eight patients with congenital anomalies, one each had severe to profound developmental delay, mild psychomotor delay and severe psychomotor delay, while the remaining five had no developmental delays. However, all three patients without congenital structural anomalies had intellectual disability (borderline intellectual functioning in one case), speech delay and global developmental delay, while motor delay and autism spectrum disorder was reported in two cases each. Isolated febrile seizure was reported in one case.

This gene has been reported in OMIM (MIM #300923) and Gene2Phenotype (with 'limited' rating) on the basis of one family from PMID:24812067.; to: PMID:24812067 reported a family in which five males spanning three generations had intellectual disability, speech delay and global developmental delay and four of these males developed seizures in late childhood–adolescence.

PMID:34346154 reported 11 unrelated cases expanding the phenotypic spectrum to include developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of clinical manifestations. Of eight patients with congenital anomalies, one each had severe to profound developmental delay, mild psychomotor delay and severe psychomotor delay, while the remaining five had no developmental delays. However, all three patients without congenital structural anomalies had intellectual disability (borderline intellectual functioning in one case), speech delay and global developmental delay, while motor delay and autism spectrum disorder was reported in two cases each. Isolated febrile seizure was reported in one case.

This gene has been reported in OMIM (MIM #300923) and Gene2Phenotype (with 'limited' rating) on the basis of one family from PMID:24812067.
Intellectual disability v5.71 KIF4A Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), there are at least four unrelated cases with hemizygous variants in KIF4A gene and presenting with intellectual disability.

PMID:24812067 reported a family in which five males spanning three generations had intellectual disability, speech delay and global developmental delay and four of these males developed seizures in late childhood–adolescence.

PMID:34346154 reported 11 unrelated cases expanding the phenotypic spectrum to include developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of clinical manifestations. Of eight patients with congenital anomalies, one each had severe to profound developmental delay, mild psychomotor delay and severe psychomotor delay, while the remaining five had no developmental delays. However, all three patients without congenital structural anomalies had intellectual disability (borderline intellectual functioning in one case), speech delay and global developmental delay, while motor delay and autism spectrum disorder was reported in two cases each. Isolated febrile seizure was reported in one case.; to: As reviewed by Zornitza Stark (Australian Genomics), there are at least four unrelated cases with hemizygous variants in KIF4A gene and presenting with intellectual disability.

PMID:24812067 reported a family in which five males spanning three generations had intellectual disability, speech delay and global developmental delay and four of these males developed seizures in late childhood–adolescence.

PMID:34346154 reported 11 unrelated cases expanding the phenotypic spectrum to include developmental delay and intellectual disability with or without epilepsy to a congenital anomaly phenotype with hydrocephalus and various brain anomalies at the more severe end of clinical manifestations. Of eight patients with congenital anomalies, one each had severe to profound developmental delay, mild psychomotor delay and severe psychomotor delay, while the remaining five had no developmental delays. However, all three patients without congenital structural anomalies had intellectual disability (borderline intellectual functioning in one case), speech delay and global developmental delay, while motor delay and autism spectrum disorder was reported in two cases each. Isolated febrile seizure was reported in one case.

This gene has been reported in OMIM (MIM #300923) and Gene2Phenotype (with 'limited' rating) on the basis of one family from PMID:24812067.
Intellectual disability v5.71 KIF4A Achchuthan Shanmugasundram reviewed gene: KIF4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24812067, 34346154; Phenotypes: ?Intellectual developmental disorder, X-linked 100, OMIM:300923; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.71 DDX23 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: DDX23.
Intellectual disability v5.71 DDX23 Achchuthan Shanmugasundram Classified gene: DDX23 as Amber List (moderate evidence)
Intellectual disability v5.71 DDX23 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS review.
Intellectual disability v5.71 DDX23 Achchuthan Shanmugasundram Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.70 DDX23 Achchuthan Shanmugasundram reviewed gene: DDX23: Rating: GREEN; Mode of pathogenicity: None; Publications: 34050707; Phenotypes: global developmental delay with speech and behavioral abnormalities, MONDO:0030995; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.70 INTS11 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: INTS11.
Intellectual disability v5.70 INTS11 Achchuthan Shanmugasundram changed review comment from: PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants.
Sources: Literature; to: PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.70 INTS11 Achchuthan Shanmugasundram Classified gene: INTS11 as Amber List (moderate evidence)
Intellectual disability v5.70 INTS11 Achchuthan Shanmugasundram Gene: ints11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.69 INTS11 Achchuthan Shanmugasundram Classified gene: INTS11 as Amber List (moderate evidence)
Intellectual disability v5.69 INTS11 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (10 unrelated cases and supporting functional evidence) for this gene to be promoted to green at the next major review.
Intellectual disability v5.69 INTS11 Achchuthan Shanmugasundram Gene: ints11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.68 INTS11 Achchuthan Shanmugasundram gene: INTS11 was added
gene: INTS11 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711
Phenotypes for gene: INTS11 were set to intellectual disability, MONDO:0001071
Review for gene: INTS11 was set to GREEN
Added comment: PMID:37054711 reported ten unrelated families with biallelic variants in INTS11 gene and they present with intellectual disability, global developmental and language delay, impaired motor development, and brain atrophy.

Functional studies in Drosophila showed that dIntS11 (fly ortholog of INTS11) is essential and expressed in the central nervous systems in a subset of neurons and most glia in larval and adult stages. In addition, genes with two variants (p.Arg17Leu and p.His414Tyr) fail to rescue the lethality of null mutants in the Drosophila model, indicating that they are strong loss-of-function variants. The other five variants (p.Gly55Ser, p.Leu138Phe, p.Lys396Glu, p.Val517Met and p.Ile553Glu) rescue lethality but cause a shortened lifespan and bang sensitivity and affect locomotor activity, indicating that they are partial loss-of-function variants.
Sources: Literature
Intellectual disability v5.67 PLK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 PLK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 PLK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram changed review comment from: Four different heterozygous variants in GRIA1 (p.Ala636Thr, p.Gly745Asp, p.Ile627Thr & p.Arg345Gln) have been identified in six unrelated individuals and they were all reported with intellectual disability, moderate to severe cognitive impairment, delayed motor development, speech impairment and behavioural issues such as anxiety, autism spectrum disorder and attention deficit hyperactivity disorder.

Homozygous variant (p.Arg377Ter) has been identified in one individual, who presented with intellectual disability, severe cognitive impairment, delayed motor development, speech impairment (non-verbal) and self-injurious behaviour.

In vitro functional studies with major GluA1-containing AMPAR subtypes carrying the GRIA1 variant mutations showed that three of the four missense variants profoundly perturb receptor function. The homozygous stop-gain variant completely destroyed the expression of GluA1-containing AMPARs. The Xenopus gria1 models also show transient motor deficits, an intermittent seizure phenotype, and a significant impairment to working memory in mutants.; to: Four different heterozygous variants in GRIA1 (p.Ala636Thr, p.Gly745Asp, p.Ile627Thr & p.Arg345Gln) have been identified in six unrelated individuals and they were all reported with intellectual disability, moderate to severe cognitive impairment, delayed motor development, speech impairment and behavioural issues such as anxiety, autism spectrum disorder and attention deficit hyperactivity disorder.

Homozygous variant (p.Arg377Ter) has been identified in one individual, who presented with intellectual disability, severe cognitive impairment, delayed motor development, speech impairment (non-verbal) and self-injurious behaviour.

In vitro functional studies with major GluA1-containing AMPAR subtypes carrying the GRIA1 variant mutations showed that three of the four missense variants profoundly perturb receptor function. The homozygous stop-gain variant completely destroyed the expression of GluA1-containing AMPARs. The Xenopus gria1 models also show transient motor deficits, an intermittent seizure phenotype, and a significant impairment to working memory in mutants.

This gene has also been associated with relevant phenotypes in both OMIM (MIM #619927 & MIM #619931) and Gene2Phenotype (with 'moderate' rating).
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Classified gene: GRIA1 as Amber List (moderate evidence)
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Gene: gria1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Classified gene: GRIA1 as Amber List (moderate evidence)
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.67 GRIA1 Achchuthan Shanmugasundram Gene: gria1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Classified gene: GRIA1 as Amber List (moderate evidence)
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Gene: gria1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Classified gene: GRIA1 as Amber List (moderate evidence)
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (6 unrelated cases with monoallelic inheritance and functional evidence including Xenopus models) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.66 GRIA1 Achchuthan Shanmugasundram Gene: gria1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Intellectual disability v5.65 GRIA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Tag watchlist was removed from gene: GRIA1.
Tag Q2_23_promote_green tag was added to gene: GRIA1.
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be monoallelic, as there is only one case identified with biallelic inheritance.
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.64 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931 to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Phenotypes for gene: GRIA1 were changed from Intellectual disability to Intellectual developmental disorder, autosomal dominant 67, OMIM:619927; ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.63 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178; 35675825
Intellectual disability v5.62 GRIA1 Achchuthan Shanmugasundram Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178
Intellectual disability v5.61 GRIA1 Achchuthan Shanmugasundram reviewed gene: GRIA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35675825; Phenotypes: Intellectual developmental disorder, autosomal dominant 67, OMIM:619927, ?Intellectual developmental disorder, autosomal recessive 76, OMIM:619931; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.61 C2orf69 Arina Puzriakova Entity copied from Mitochondrial disorders v4.27
Intellectual disability v5.61 C2orf69 Arina Puzriakova gene: C2orf69 was added
gene: C2orf69 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review Amber,Literature
Q2_23_promote_green tags were added to gene: C2orf69.
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency 53, OMIM:619423
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TAF2.
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.60 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Classified gene: TAF2 as Amber List (moderate evidence)
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least 4 unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Gene: taf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.59 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 22633631; 24084144; 26350204; 34474177
Intellectual disability v5.58 TAF2 Achchuthan Shanmugasundram Publications for gene: TAF2 were set to 21937992; 24084144; 26350204
Intellectual disability v5.57 TAF2 Achchuthan Shanmugasundram reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 24084144, 34474177; Phenotypes: Mental retardation, autosomal recessive 40, OMIM:615599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SHANK1.
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Classified gene: SHANK1 as Amber List (moderate evidence)
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Gene: shank1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Classified gene: SHANK1 as Amber List (moderate evidence)
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.57 SHANK1 Achchuthan Shanmugasundram Gene: shank1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Classified gene: SHANK1 as Amber List (moderate evidence)
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Gene: shank1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Classified gene: SHANK1 as Amber List (moderate evidence)
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (at least four unrelated cases) for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.56 SHANK1 Achchuthan Shanmugasundram Gene: shank1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.55 SHANK1 Achchuthan Shanmugasundram Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.55 SHANK1 Achchuthan Shanmugasundram Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.55 SHANK1 Achchuthan Shanmugasundram Phenotypes for gene: SHANK1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.55 SHANK1 Achchuthan Shanmugasundram Phenotypes for gene: SHANK1 were changed from AUTISM to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.54 SHANK1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Zornitza Stark (Australian Genomics), PMID:34113010 reported six individuals who presented with neurodevelopmental disorders and identified with de novo truncating variants in SHANK1 gene. Of these six individuals, four had intellectual disability, one had severe learning difficulties and one with auditory processing disorder, difficulty with executive functioning, mathematic concepts, verbal reasoning and problem solving.; to: As reviewed by Zornitza Stark (Australian Genomics), PMID:34113010 reported six unrelated individuals who presented with neurodevelopmental disorders and identified with de novo truncating variants in SHANK1 gene. Of these six individuals, four had intellectual disability, one had severe learning difficulties and one with auditory processing disorder, difficulty with executive functioning, mathematic concepts, verbal reasoning and problem solving. Three of these patients were also reported with autism spectrum disorder.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.54 SHANK1 Achchuthan Shanmugasundram Publications for gene: SHANK1 were set to 0
Intellectual disability v5.53 SHANK1 Achchuthan Shanmugasundram edited their review of gene: SHANK1: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.53 SHANK1 Achchuthan Shanmugasundram edited their review of gene: SHANK1: Added comment: As reviewed by Zornitza Stark (Australian Genomics), PMID:34113010 reported six individuals who presented with neurodevelopmental disorders and identified with de novo truncating variants in SHANK1 gene. Of these six individuals, four had intellectual disability, one had severe learning difficulties and one with auditory processing disorder, difficulty with executive functioning, mathematic concepts, verbal reasoning and problem solving.; Changed phenotypes to: nearodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.53 SHANK1 Achchuthan Shanmugasundram reviewed gene: SHANK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34113010; Phenotypes: neurocde; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots (RadboudUMC), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots (RadboudUMC), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots (RadboudUMC), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Classified gene: PLK1 as Amber List (moderate evidence)
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots (RadboudUMC), there is sufficient evidence for this gene to be promoted to GREEN at the next major review.
Intellectual disability v5.53 PLK1 Achchuthan Shanmugasundram Gene: plk1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.52 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Intellectual disability v5.52 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Intellectual disability v5.52 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Intellectual disability v5.51 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to 33875846
Intellectual disability v5.51 PLK1 Achchuthan Shanmugasundram Publications for gene: PLK1 were set to PMID: 33875846
Intellectual disability v5.50 PLK1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PLK1.
Intellectual disability v5.50 PLK1 Achchuthan Shanmugasundram reviewed gene: PLK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33875846; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram changed review comment from: PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.; to: PMID:31997314 reported a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy and was identified with homozygous variant in OTUD7A gene (c.697C>T)/ p.Leu233Phe).

PMID:33381903 reported a patient with profound hypotonia, severe intellectual disability, and seizures and identified with biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del/ p.Glu375Aspfs*11.

PMID:36180924 reported a patient (patient #4) presenting with severe neurodevelopmental diseases and dysmorphic features and identified with hemizygous OTUD7A frameshift variant allele c.2023_2066del/ p.D675Hfs*188 in trans with the recurrent 15q13.3 BP4-BP5 deletion.

OTUD7A knockout mice exhibited reduced body weight, developmental delay, abnormal electroencephalography patterns and seizures, reduced ultrasonic vocalisations, decreased grip strength, impaired motor learning/motor coordination, and reduced acoustic startle (PMID:29395075). The function evidence also suggest that OTUD7A may be the critical “driver gene” in the 15q13.3 deletion syndrome.

This gene has been reported in the DD panel of Gene2Phenotype (with 'limited' rating), but has not yet been associated with phenotypes in OMIM.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.51 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: OTUD7A.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Classified gene: OTUD7A as Amber List (moderate evidence)
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated cases with biallelic variants and supportive functional evidence from mouse models) for this gene to be promoted to green at the next major review.
Intellectual disability v5.50 OTUD7A Achchuthan Shanmugasundram Gene: otud7a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.49 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.48 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074; 33381903; 36180924
Intellectual disability v5.48 OTUD7A Achchuthan Shanmugasundram Publications for gene: OTUD7A were set to 31997314; 29395075; 29395074
Intellectual disability v5.47 OTUD7A Achchuthan Shanmugasundram reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29395075, 31997314, 33381903, 36180924; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.47 CLCN4 Arina Puzriakova Phenotypes for gene: CLCN4 were changed from Mental retardation, X-linked 49-15 300114 to Raynaud-Claes syndrome, OMIM:300114
Intellectual disability v5.46 PDHX Arina Puzriakova Phenotypes for gene: PDHX were changed from Lacticacidemia due to PDX1 deficiency 245349 to Lacticacidemia due to PDX1 deficiency, OMIM:245349
Intellectual disability v5.45 PDHB Arina Puzriakova Phenotypes for gene: PDHB were changed from Pyruvate dehydrogenase E1-beta deficiency, MIM#614111 to Pyruvate dehydrogenase E1-beta deficiency, OMIM:614111
Intellectual disability v5.44 PC Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency, 266150; PYRUVATE CARBOXYLASE DEFICIENCY (PC DEFICIENCY) to Pyruvate carboxylase deficiency, OMIM:266150
Intellectual disability v5.43 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, 252010; LEIGH SYNDROME (NUCLEAR DNA MUTATION) to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Intellectual disability v5.42 DARS2 Arina Puzriakova Phenotypes for gene: DARS2 were changed from Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105; LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105
Intellectual disability v5.41 SUCLA2 Arina Puzriakova Phenotypes for gene: SUCLA2 were changed from Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria); OMIM #612073 to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Intellectual disability v5.40 NADK2 Arina Puzriakova Phenotypes for gene: NADK2 were changed from ?2,4-dienoyl-CoA reductase deficiency to 2,4-dienoyl-CoA reductase deficiency, OMIM:616034
Intellectual disability v5.39 COX14 Arina Puzriakova Mode of inheritance for gene: COX14 was changed from MITOCHONDRIAL to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.38 NAPB Arina Puzriakova Phenotypes for gene: NAPB were changed from Early infantile epileptic encephalopathy to Developmental and epileptic encephalopathy 107, OMIM:620033
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.37 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.

In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram changed review comment from: There are more than 20 unrelated cases identified with variants in IQSEC2 gene, as reported in publications. Moderate to severe intellectual disability was present in all affected males.

De novo, truncating variants correlate with severe disease in both female and male patients harboring an IQSEC2 alteration. Missense variants in male and female patients account for a milder disease overall, with more severe symptoms in males than females. This evidence suggests that the MOI should be 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.

Both OMIM and Gene2Phenotype have associated X-linked dominant variants in IQSEC2 with intellectual disability (MIM #309530); to: There are more than 20 unrelated cases identified with variants in IQSEC2 gene, as reported in publications. Moderate to severe intellectual disability was present in all affected males.

De novo, truncating variants correlate with severe disease in both female and male patients harboring an IQSEC2 alteration. Missense variants in male and female patients account for a milder disease overall, with more severe symptoms in males than females.
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.36 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Intellectual disability v5.35 IQSEC2 Achchuthan Shanmugasundram Publications for gene: IQSEC2 were set to
Intellectual disability v5.34 IQSEC2 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: IQSEC2.
Intellectual disability v5.34 IQSEC2 Achchuthan Shanmugasundram reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20473311, 23674175, 30842726, 31415821, 33368194; Phenotypes: Intellectual developmental disorder, X-linked 1, OMIM: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 v5.34 HUWE1 Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: HUWE1.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene from 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene from 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene from 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.; to: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene from 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene from 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene from 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for updating the MOI of this gene from 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)'.
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Mode of inheritance for gene: HUWE1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.34 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.33 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to 7943042; 18252223; 24896178; 25529582; 29180823
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Publications for gene: HUWE1 were set to
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.32 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590 to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.31 HUWE1 Achchuthan Shanmugasundram Phenotypes for gene: HUWE1 were changed from Mental retardation, X-linked syndromic, Turner type, 300706; MENTAL RETARDATION SYNDROMIC X-LINKED TURNER TYPE (MRXST) to Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590
Intellectual disability v5.30 HUWE1 Achchuthan Shanmugasundram reviewed gene: HUWE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29180823; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Turner type, OMIM:309590; 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 v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Classified gene: TRAPPC10 as Amber List (moderate evidence)
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are only two unrelated cases with intellectual disability and global developmental delay. Although there are functional studies available, no cognitive defects were reported in the mouse model.

The 'watchlist' tag has been added to review this gene rating regularly in light of any new evidence.
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Gene: trappc10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.30 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: TRAPPC10.
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.29 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.28 TRAPPC10 Achchuthan Shanmugasundram Phenotypes for gene: TRAPPC10 were changed from Intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.27 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849; 35298461
Intellectual disability v5.26 TRAPPC10 Achchuthan Shanmugasundram Publications for gene: TRAPPC10 were set to 30167849
Intellectual disability v5.25 TRAPPC10 Achchuthan Shanmugasundram reviewed gene: TRAPPC10: Rating: AMBER; Mode of pathogenicity: None; Publications: 30167849, 35298461; Phenotypes: Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Tracy Lester (Genetics laboratory, Oxford UK), there is sufficient evidence for this gene to be promoted to GREEN in the next major review.

This gene can be associated with both monoallelic and biallelic inheritance as there are at least three cases each for both of them.; to: Comment on list classification:, There is sufficient evidence for this gene to be promoted to GREEN at the next major review.

This gene can be associated with both monoallelic and biallelic inheritance as there are at least three cases each for both of them.
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: KDM5A.
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: KDM5A.
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.25 KDM5A Achchuthan Shanmugasundram Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Intellectual disability v5.24 KDM5A Achchuthan Shanmugasundram changed review comment from: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.

In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice.; to: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.

In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice.

This gene has already been associated with phenotype in Gene2Phenotype (biallelic inheritance with 'limited' rating), but not in OMIM.
Intellectual disability v5.24 KDM5A Achchuthan Shanmugasundram Classified gene: KDM5A as Amber List (moderate evidence)
Intellectual disability v5.24 KDM5A Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester (Genetics laboratory, Oxford UK), there is sufficient evidence for this gene to be promoted to GREEN in the next major review.

This gene can be associated with both monoallelic and biallelic inheritance as there are at least three cases each for both of them.
Intellectual disability v5.24 KDM5A Achchuthan Shanmugasundram Gene: kdm5a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.23 KDM5A Achchuthan Shanmugasundram changed review comment from: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.; to: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.

In addition, loss of KDM5A has resulted in repetitive behaviors, sociability deficits, cognitive dysfunction, and abnormal dendritic morphogenesis in mice.
Intellectual disability v5.23 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.23 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.22 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992; 33350388
Intellectual disability v5.21 KDM5A Achchuthan Shanmugasundram Publications for gene: KDM5A were set to 21937992
Intellectual disability v5.21 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.21 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.21 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.20 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.20 KDM5A Achchuthan Shanmugasundram Mode of inheritance for gene: KDM5A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.19 KDM5A Achchuthan Shanmugasundram changed review comment from: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech and developmental delay.; to: PMID:21937992 reported a family with recessive missense KDM5A variant presenting with an undefined developmental disorder characterised with intellectual disability and facial dysmorphisms.

PMID:33350388 reported nine patients from seven unrelated families identified with variants in KDM5A, of which three unrelated patients harboured heterozygous variants, while six patients from four unrelated families had homozygous variants. These patients presented with autism spectrum disorder (ASD) and a spectrum of neurodevelopmental phenotypes including intellectual disability, lack of speech, developmental delay and motor impairment.
Intellectual disability v5.19 KDM5A Achchuthan Shanmugasundram reviewed gene: KDM5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 33350388; Phenotypes: autism spectrum disorder, MONDO:0005258, intellectual disability, MONDO:0001071; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.19 SPG7 Sarah Leigh commented on gene: SPG7
Intellectual disability v5.19 SPG7 Sarah Leigh Publications for gene: SPG7 were set to 22571692
Intellectual disability v5.18 SPG7 Sarah Leigh Mode of inheritance for gene: SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability v5.17 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Intellectual disability v5.16 SPTAN1 Sarah Leigh Phenotypes for gene: SPTAN1 were changed from Epileptic encephalopathy, early infantile, 5, 613477; EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 5 (EIEE5) to Developmental and epileptic encephalopathy 5, OMIM:613477; developmental and epileptic encephalopathy, 5, MONDO:0013277
Intellectual disability v5.15 SPTAN1 Sarah Leigh Publications for gene: SPTAN1 were set to
Intellectual disability v5.14 NFASC Sarah Leigh Phenotypes for gene: NFASC were changed from Neurodevelopmental disorder with central and peripheral motor dysfunction 618356 to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; neurodevelopmental disorder with central and peripheral motor dysfunction, MONDO:003269
Intellectual disability v5.13 MED11 Sarah Leigh Classified gene: MED11 as Amber List (moderate evidence)
Intellectual disability v5.13 MED11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.13 MED11 Sarah Leigh Gene: med11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.12 MED11 Sarah Leigh gene: MED11 was added
gene: MED11 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: MED11.
Mode of inheritance for gene: MED11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED11 were set to 36001086
Phenotypes for gene: MED11 were set to MED11-associated neurodevelopmental disorder
Review for gene: MED11 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, but is associated with MED11-associated neurodevelopmental disorder in Gen2Phen. PMID: 36001086 reports a single MED11 variant (NM_001001683.4: c.325C>T, p.Arg109*), that segregates with the condition in five unrelated families, however, there is homozygosity between two of these families, idicating that they may be related. Global delay was observed in three individuals from three unrelated familes and seizures were evident in four individuals from four unrelated families. Severe microcephaly was apparent in the two unrelated familes where this parameter was recorded. Overall, the MED11-associated neurodevelopmental disorder appeared to result in profound effects and proved fatal at birth and 10 days in two of the cases reported.
Sources: Literature
Intellectual disability v5.11 KDM5A Tracy Lester reviewed gene: KDM5A: Rating: AMBER; Mode of pathogenicity: None; Publications: 33350388; Phenotypes: ASD, lack of speech; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.; to: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and the association is supported by functional studies from mouse models. This gene therefore has sufficient evidence for promotion to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.; to: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.11 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: UBAP2L.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Classified gene: UBAP2L as Amber List (moderate evidence)
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are at least 8 unrelated cases that had borderline to severe intellectual disability (ID) as identified with formal intellectual evaluation and supported by functional studies from mouse models. This gene therefore has sufficient evidence for promoting to green at the next major review.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype with a 'moderate rating'.
Intellectual disability v5.10 UBAP2L Achchuthan Shanmugasundram Gene: ubap2l has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.; to: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases and supporting functional evidence) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.9 CAPRIN1 Achchuthan Shanmugasundram Mode of inheritance for gene: CAPRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.8 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.7 CAPRIN1 Achchuthan Shanmugasundram Publications for gene: CAPRIN1 were set to 23849776
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CAPRIN1.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Classified gene: CAPRIN1 as Amber List (moderate evidence)
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As indicated by the previous reviewers, there is sufficient evidence (>10 unrelated cases) for this gene to be promoted to GREEN at the next major review.

However, this gene has not yet been associated with relevant phenotypes in OMIM, but it has been reported in Gene2Phenotype with 'moderate' rating.
Intellectual disability v5.6 CAPRIN1 Achchuthan Shanmugasundram Gene: caprin1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.5 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862; 36345169
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:36345169 reported a paediatric patient identified with a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. This patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis shows that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations.
Intellectual disability v5.4 ARF1 Achchuthan Shanmugasundram Publications for gene: ARF1 were set to 28868155; 34353862
Intellectual disability v5.3 FEM1C Achchuthan Shanmugasundram Publications for gene: FEM1C were set to 36336956
Intellectual disability v5.2 FEM1C Achchuthan Shanmugasundram edited their review of gene: FEM1C: Changed publications to: 28135719, 36336956
Intellectual disability v5.2 FEM1C Achchuthan Shanmugasundram gene: FEM1C was added
gene: FEM1C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: FEM1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEM1C were set to 36336956
Phenotypes for gene: FEM1C were set to Intellectual disability, MONDO:0001071
Review for gene: FEM1C was set to RED
Added comment: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2023-03-22
Intellectual disability v5.0 Arina Puzriakova promoted panel to version 5.0
Intellectual disability v4.127 HIST1H4E Eleanor Williams commented on gene: HIST1H4E
Intellectual disability v4.126 Arina Puzriakova Panel name changed from Intellectual disability to Intellectual disability - microarray and sequencing
List of related panels changed from Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; R29 to Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability; R29
Intellectual disability v4.125 ATP9A Eleanor Williams Tag gene-checked was removed from gene: ATP9A.
Intellectual disability v4.125 ATP9A Eleanor Williams Added comment: Comment on phenotypes: Adding the OMIM phenotype which was added to OMIM in Feb 2023.
Intellectual disability v4.125 ATP9A Eleanor Williams Phenotypes for gene: ATP9A were changed from Global developmental delay; Intellectual disability; Postnatal microcephaly; Failure to thrive; Abnormality of the abdomen to Global developmental delay; Intellectual disability; Postnatal microcephaly; Failure to thrive; Abnormality of the abdomen; Neurodevelopmental disorder with poor growth and behavioral abnormalities, OMIM:620242
Intellectual disability v4.124 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.124 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.123 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to 35971781
Intellectual disability v4.123 TAB2 Achchuthan Shanmugasundram Publications for gene: TAB2 were set to
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.122 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Classified gene: TAB2 as Amber List (moderate evidence)
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER. Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and the majority of cases in PMID:35971781 and other previous studies were not reported with ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.
Intellectual disability v4.121 TAB2 Achchuthan Shanmugasundram Gene: tab2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.120 TAB2 Achchuthan Shanmugasundram changed review comment from: 4 out of 14 patients identified with heterozygous variants in TAB2 gene in PMID:35971781 were reported with global developmental delay and intellectual disability (ID). Two other patients were reported with motor delay. Although developmental delay was reported in previous studies including the one reviewed by Andrea Haworth below, none of the previous studies reported cases with ID.

Although there are four unrelated cases reported with ID, ID is part of a broad spectrum of phenotypes and a majority of cases in this study and other previous studies did not report ID as part of the phenotype.

ID has not been reported as part of the phenotype either in OMIM or in Gene2Phenotype.; to: 4 out of 14 patients identified with heterozygous variants in TAB2 gene in PMID:35971781 were reported with global developmental delay and intellectual disability (ID). Two other patients were reported with motor delay. Although developmental delay was reported in previous studies including the one reviewed by Andrea Haworth below, none of the previous studies reported cases with ID.
Intellectual disability v4.120 TAB2 Achchuthan Shanmugasundram reviewed gene: TAB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35971781; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.120 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587; 36255738
Intellectual disability v4.119 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.118 KPTN Sarah Leigh Phenotypes for gene: KPTN were changed from MACROCEPHALY, NEURODEVELOPMENTAL DELAY, AND SEIZURES to Intellectual developmental disorder, autosomal recessive 41, OMIM:615637; macrocephaly-developmental delay syndrome, MONDO:0014289
Intellectual disability v4.117 TBX1 Arina Puzriakova reviewed gene: TBX1: Rating: ; Mode of pathogenicity: None; Publications: 14585638, 17273972, 30137364; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GCSH.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.116 GCSH Achchuthan Shanmugasundram Phenotypes for gene: GCSH were changed from Glycine encephalopathy to ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to 36190515
Intellectual disability v4.115 GCSH Achchuthan Shanmugasundram Publications for gene: GCSH were set to
Intellectual disability v4.114 GCSH Achchuthan Shanmugasundram reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 36190515; Phenotypes: ?Glycine encephalopathy, OMIM:605899, Neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.113 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.114 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.113 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697; 36226587
Intellectual disability v4.112 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.113 SUPT16H Achchuthan Shanmugasundram Publications for gene: SUPT16H were set to 31924697
Intellectual disability v4.112 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.112 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.111 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.111 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.111 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.111 SUPT16H Achchuthan Shanmugasundram Phenotypes for gene: SUPT16H were changed from Global developmental delay; Intellectual disability; Abnormality of the corpus callosum to Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum, OMIM:619480; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum
Intellectual disability v4.110 YWHAZ Achchuthan Shanmugasundram gene: YWHAZ was added
gene: YWHAZ was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: YWHAZ was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: YWHAZ were set to 36001342
Phenotypes for gene: YWHAZ were set to Intellectual disability, MONDO:0001071
Review for gene: YWHAZ was set to RED
Added comment: PMID:36001342 reported one large three-generation family with intellectual disability and global developmental delay, where all affected members were identified with a heterozygous missense variant (c.147A>T/ p.Lys49Asn) in YWHAZ gene. Although there were 10 other rare variants located in 10 genes (ARHGAP4, AGPS, APOL3, CES3, DACT2, ECH1, FAM71E2, KREMEN1, YWHAZ, ZFYVE26) that co-segregated with the ID/GDD phenotype were identified in the family, they were either not present in all affected members or present in unaffected members.

In addition, computational modeling and knockdown/ knockin studies with Drosophila also confirmed the role of this YWHAZ variant in intellectual disability.
Sources: Literature
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.110 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.110 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.108 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407; 35981081
Intellectual disability v4.109 DEAF1 Achchuthan Shanmugasundram Phenotypes for gene: DEAF1 were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 24; ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828 to ?Dyskinesia, seizures, and intellectual developmental disorder, 617171; Mental retardation, autosomal dominant 24, 615828
Intellectual disability v4.108 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407; 35981081
Intellectual disability v4.108 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407; 35981081
Intellectual disability v4.107 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407; 35981081
Intellectual disability v4.107 DEAF1 Achchuthan Shanmugasundram Publications for gene: DEAF1 were set to 21076407
Intellectual disability v4.106 SARS Arina Puzriakova Classified gene: SARS as Amber List (moderate evidence)
Intellectual disability v4.106 SARS Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated cases with biallelic variants in this gene - DD/ID detected in all families.
Intellectual disability v4.106 SARS Arina Puzriakova Gene: sars has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.105 SARS Arina Puzriakova Phenotypes for gene: SARS were changed from ?Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709 to Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709
Intellectual disability v4.104 SARS Arina Puzriakova Publications for gene: SARS were set to 28236339; 34570399
Intellectual disability v4.103 SARS Arina Puzriakova Tag watchlist was removed from gene: SARS.
Tag Q1_23_promote_green tag was added to gene: SARS.
Intellectual disability v4.103 SARS Arina Puzriakova reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CTR9.
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Classified gene: CTR9 as Amber List (moderate evidence)
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are sufficient unrelated cases (at least 10) reported with varying degrees (mild to severe) intellectual disability.
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Gene: ctr9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Phenotypes for gene: CTR9 were changed from Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system to Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system
Intellectual disability v4.103 CTR9 Achchuthan Shanmugasundram Phenotypes for gene: CTR9 were changed from Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system to Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Phenotypes for gene: CTR9 were changed from Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system to Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system
Intellectual disability v4.102 CTR9 Achchuthan Shanmugasundram Phenotypes for gene: CTR9 were changed from Delayed speech and language development; Motor delay; Intellectual disability; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system to Macrocephaly, HP:0000256; Motor delay, HP:0001270; intellectual disability, MONDO:0001071; Delayed speech and language development; Behavioral abnormality; Autistic behavior; Failure to thrive; Feeding difficulties; Abnormality of the cardiovascular system
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.101 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 35717577
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.100 CTR9 Achchuthan Shanmugasundram Publications for gene: CTR9 were set to 35499524; 2815719; 25363760; 27479843; 25099282; 29292210
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.99 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.97 CTR9 Achchuthan Shanmugasundram Mode of inheritance for gene: CTR9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from None to None
Intellectual disability v4.98 CTR9 Achchuthan Shanmugasundram Mode of pathogenicity for gene: CTR9 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Intellectual disability v4.97 CTR9 Achchuthan Shanmugasundram Mode of inheritance for gene: CTR9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.97 CTR9 Achchuthan Shanmugasundram Mode of inheritance for gene: CTR9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.97 CTR9 Achchuthan Shanmugasundram Mode of inheritance for gene: CTR9 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.96 CTR9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.96 CTR9 Achchuthan Shanmugasundram edited their review of gene: CTR9: Added comment: As noted by the reviewer, PMID: 35499524 reported 13 unrelated cases identified with heterozygous variants in CTR9 gene (11 different variants) and they presented with overlapping neurodegenerative phenotypes including intellectual disability, hypotonia, joint hyperlaxity, speech delay, coordination problems, tremor, and autism spectrum disorder. Mild dysmorphism and cardiac anomalies were less frequent. The intellect levels were determined only for 11 patients (the rest are too young) and 8 out of these 11 patients were reported with variable degree of intellectual disability, while other three had impairments in other domains or learning difficulties.

PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in zebrafish also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).

This gene has not yet been associated with relevant phenotypes in OMIM. It has been associated with Wilms tumour in Gene2Phenotype (phenotype not relevant to this panel).; Changed rating: GREEN; Changed publications to: 35499524, 35717577
Intellectual disability v4.96 CTR9 Achchuthan Shanmugasundram edited their review of gene: CTR9: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.96 CTR9 Achchuthan Shanmugasundram edited their review of gene: CTR9: Changed phenotypes to: Macrocephaly, HP:0000256, Motor delay, HP:0001270, intellectual disability, MONDO:0001071
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated GREEN as bi-allelic variants in RBSN has been associated with a phenotype encompassing developmental delay and intellectual disability from four unrelated families.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.; to: Comment on list classification: This gene should be rated GREEN as bi-allelic variants in RBSN has been associated with a phenotype encompassing developmental delay and intellectual disability from four unrelated families.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: RBSN.
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Classified gene: RBSN as Amber List (moderate evidence)
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as bi-allelic variants in RBSN has been associated with a phenotype encompassing developmental delay and intellectual disability from four unrelated families.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Gene: rbsn has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Classified gene: RBSN as Amber List (moderate evidence)
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as bi-allelic variants in RBSN has been associated with a phenotype encompassing developmental delay and intellectual disability from four unrelated families.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v4.96 RBSN Achchuthan Shanmugasundram Gene: rbsn has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.95 RBSN Achchuthan Shanmugasundram gene: RBSN was added
gene: RBSN was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: RBSN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBSN were set to 25233840; 29784638; 35652444
Phenotypes for gene: RBSN were set to intellectual disability, MONDO:0001071
Review for gene: RBSN was set to GREEN
Added comment: PMID:25233840 reported a 6.5 year old female patient with a homozygous missense variant c.1273G > A (p.Gly425Arg) and her clinical presentation included intractable seizures, developmental delay, microcephaly, dysostosis, osteopenia, craniofacial dysmorphism, macrocytosis and megaloblastoid erythropoiesis.

PMID:29784638 reported three siblings with homozygous variant c.289G>C (p.Gly97Arg) in RBSN. The proband presented global developmental delay, had complete 46,XY male-to-female sex reversal and died at age 20 months after multiple infections. The other 2 affected siblings underwent unrelated-donor bone marrow or stem cell transplantation at 8 and 6.5 months of age, respectively. Both have severe intellectual disability and are nonambulatory and nonverbal.

PMID:35652444 reported two unrelated families (three siblings from a family of Iranian descent identified with homozygous variant c.547G>A (p.Gly183Arg) and four members from a family of indigenous Cree descent identified with homozygous variant c.538C>G (p.Arg180Gly)) with overlapping phenotypes including developmental delay, intellectual disability, distal motor axonal neuropathy and facial dysmorphism.
Sources: Literature
Intellectual disability v4.94 CTR9 Achchuthan Shanmugasundram changed review comment from: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).

This gene has not yet been associated with relevant phenotypes in OMIM. It has been associated with Wilms tumour in Gene2Phenotype (phenotype not relevant to this panel).; to: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in zebrafish also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).

This gene has not yet been associated with relevant phenotypes in OMIM. It has been associated with Wilms tumour in Gene2Phenotype (phenotype not relevant to this panel).
Intellectual disability v4.94 DPYSL2 Achchuthan Shanmugasundram Classified gene: DPYSL2 as Amber List (moderate evidence)
Intellectual disability v4.94 DPYSL2 Achchuthan Shanmugasundram Gene: dpysl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.94 DPYSL2 Achchuthan Shanmugasundram Classified gene: DPYSL2 as Amber List (moderate evidence)
Intellectual disability v4.94 DPYSL2 Achchuthan Shanmugasundram Gene: dpysl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.93 DPYSL2 Achchuthan Shanmugasundram changed review comment from: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients.

PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus.

It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype.

Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability.
Sources: Literature; to: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients.

PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus.

It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype.

Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v4.93 DPYSL2 Achchuthan Shanmugasundram gene: DPYSL2 was added
gene: DPYSL2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: DPYSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DPYSL2 were set to 27249678; 35861646
Phenotypes for gene: DPYSL2 were set to intellectual disability, MONDO:0001071; Aplasia/Hypoplasia of the corpus callosum, HP:0007370
Review for gene: DPYSL2 was set to AMBER
Added comment: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients.

PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus.

It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype.

Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability.
Sources: Literature
Intellectual disability v4.92 CTR9 Achchuthan Shanmugasundram changed review comment from: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).; to: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).

This gene has not yet been associated with relevant phenotypes in OMIM. It has been associated with Wilms tumour in Gene2Phenotype (phenotype not relevant to this panel).
Intellectual disability v4.92 CTR9 Achchuthan Shanmugasundram edited their review of gene: CTR9: Added comment: PMID:35717577 reported two additional unrelated cases with non-synonymous heterozygous CTR9 variants (p.Glu15Asp and p.Pro25Arg) and they presented with macrocephaly, motor delay, and intellectual disability. In addition, functional studies in also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).; Changed phenotypes to: Macrocephaly, HP:0000256, Motor delay, HP:0001270, intellectual disability, MONDO_0001071
Intellectual disability v4.92 CTR9 Achchuthan Shanmugasundram reviewed gene: CTR9: Rating: AMBER; Mode of pathogenicity: None; Publications: 35717577; Phenotypes: Macrocephaly, HP:0000256, Motor delay, HP:0001270, intellectual disability, MONDO_000107; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.92 NUP214 Eleanor Williams changed review comment from: Associated with {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426 in OMIM and Gene2Phenotype (probable).

PMID: 31178128 - Fichtman et al 2019 - report on two families one of Palestinian decent, the other Northern European (not Finnish descent). Each had two affected siblings in which neurological decline was seen after febrile events. The older son in family A, exhibited minor developmental delay from infancy. A homozygous missense variant was identified in NUP214 (p.Arg38Cys) in family A and segregated with the disease in available family members. In family B affected sisters were compound heterozygous for a frameshift and a missense variant in NUP214 (p.Pro387Ser and p.Pro525Leufs∗6). Functional studies with fibroblasts from one patient in family A showed a decrease in NUP214 and NUP88 levels compared to controls,

PMID: 30758658 - Shamseldin et al 2019 - describe a multiplex consanguineous family in which four affected members presented with severe neonatal hypotonia, profound global developmental delay, progressive microcephaly and early death (<2 year old). Whole exome sequencing revealed the presence of a novel homozygous missense variant in NUP214, p.D154G.

PMID: 29483668 - Egloff et al 2018 - report a 4-year-old girl presenting with developmental delay, growth retardation and facial dysmorphism. She was found to have a 9q deletion inherited from her healthy mother and a hemizygous one-base pair deletion in the NUP214 gene inherited from her father. From patient leukocytes it was found that the expression level of the NUP214 transcript was significantly decreased and close to zero in the patient compared to the controls. ; to: Associated with {Encephalopathy, acute, infection-induced, susceptibility to, 9} 618426 in OMIM and Gene2Phenotype (probable).

PMID: 31178128 - Fichtman et al 2019 - report on two families one of Palestinian decent, the other Northern European (not Finnish descent). Each had two affected family members in which neurological decline was seen after febrile events. The older son in family A, exhibited minor developmental delay from infancy. A homozygous missense variant was identified in NUP214 (p.Arg38Cys) in family A and segregated with the disease in available family members. In family B affected sisters were compound heterozygous for a frameshift and a missense variant in NUP214 (p.Pro387Ser and p.Pro525Leufs∗6). Functional studies with fibroblasts from one patient in family A showed a decrease in NUP214 and NUP88 levels compared to controls,

PMID: 30758658 - Shamseldin et al 2019 - describe a multiplex consanguineous family in which four affected members presented with severe neonatal hypotonia, profound global developmental delay, progressive microcephaly and early death (<2 year old). Whole exome sequencing revealed the presence of a novel homozygous missense variant in NUP214, p.D154G.

PMID: 29483668 - Egloff et al 2018 - report a 4-year-old girl presenting with developmental delay, growth retardation and facial dysmorphism. She was found to have a 9q deletion inherited from her healthy mother and a hemizygous one-base pair deletion in the NUP214 gene inherited from her father. From patient leukocytes it was found that the expression level of the NUP214 transcript was significantly decreased and close to zero in the patient compared to the controls.
Intellectual disability v4.92 NUP214 Eleanor Williams edited their review of gene: NUP214: Changed publications to: 31178128, 30758658, 29483668
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Classified gene: SEMA6B as Amber List (moderate evidence)
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Gene: sema6b has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Classified gene: SEMA6B as Amber List (moderate evidence)
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Gene: sema6b has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: SEMA6B.
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Classified gene: SEMA6B as Amber List (moderate evidence)
Intellectual disability v4.92 SEMA6B Achchuthan Shanmugasundram Gene: sema6b has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.91 SEMA6B Achchuthan Shanmugasundram gene: SEMA6B was added
gene: SEMA6B was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: SEMA6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA6B were set to 35604360
Phenotypes for gene: SEMA6B were set to Intellectual disability, MONDO:0001071
Review for gene: SEMA6B was set to GREEN
Added comment: Comment on gene classification: This gene should be rated GREEN in this panel as monoallelic variants in this gene has been associated with a final diagnosis of intellectual disability (ID) in 11 unrelated cases.

PMID:35604360 reports 14 heterozygous variants (11 novel and 3 previously reported variants) observed in 16 unrelated individuals referred for ID. Out of these, 11 of them had a final diagnosis of ID. Heterozygous variants in SEMA6B has previously been reported in patients with progressive myoclonic epilepsy (MIM #618876) and there were no cases of ID reported before. This study indicated that the clinical spectrum is wider and included ID without epilepsy or myoclonus.

Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.
Sources: Literature
Intellectual disability v4.90 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.90 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.90 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.90 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.89 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.89 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.89 EMC1 Achchuthan Shanmugasundram Phenotypes for gene: EMC1 were changed from Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM 616875; Cerebellar atrophy, visual impairment, and psychomotor retardation, 616875 to Cerebellar atrophy, visual impairment, and psychomotor retardation, OMIM:616875
Intellectual disability v4.88 CPLX1 Sarah Leigh Entity copied from Genetic epilepsy syndromes v3.90
Intellectual disability v4.88 CPLX1 Sarah Leigh gene: CPLX1 was added
gene: CPLX1 was added to Intellectual disability. Sources: Expert list,Expert Review Amber
Q1_23_promote_green tags were added to gene: CPLX1.
Mode of inheritance for gene: CPLX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPLX1 were set to 26539891; 28422131
Phenotypes for gene: CPLX1 were set to Developmental and epileptic encephalopathy 63, OMIM:617976; developmental and epileptic encephalopathy, 63, MONDO:0033372
Intellectual disability v4.87 STXBP1 Sarah Leigh Tag Q1_23_MOI tag was added to gene: STXBP1.
Intellectual disability v4.87 STXBP1 Sarah Leigh Added comment: Comment on mode of inheritance: Due to the report of biallelic STXBP1 variants in a family with encephalopathy, developmental delay, intellectual disability and epilepsy (PMID: 31855252), the mode of inheritance for this gene should be changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Intellectual disability v4.87 STXBP1 Sarah Leigh Mode of inheritance for gene: STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.86 STXBP1 Sarah Leigh Phenotypes for gene: STXBP1 were changed from Epileptic encephalopathy, early infantile, 4, 612164 (2); ANGELMAN/PITT HOPKINS SYNDROME-LIKE DISORDER to Developmental and epileptic encephalopathy 4, OMIM:612164; developmental and epileptic encephalopathy, 4, MONDO:0012812
Intellectual disability v4.85 STXBP1 Sarah Leigh Publications for gene: STXBP1 were set to 31855252; 18469812; 19557857
Intellectual disability v4.84 STXBP1 Sarah Leigh Publications for gene: STXBP1 were set to
Intellectual disability v4.83 STXBP1 Sarah Leigh reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 29633245; 31209944; 31350873; 35512351
Intellectual disability v4.83 TASP1 Achchuthan Shanmugasundram Publications for gene: TASP1 were set to 31209944; 31350873
Intellectual disability v4.82 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.82 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.82 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.82 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.81 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.81 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.81 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Suleiman-El-Hattab syndrome, OMIM:618950 to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.81 TASP1 Achchuthan Shanmugasundram Phenotypes for gene: TASP1 were changed from Developmental delay; microcephaly; dysmorphic features; congenital abnormalities to Suleiman-El-Hattab syndrome, OMIM:618950
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.81 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.81 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.81 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.81 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267; 36301021; 36646976
Intellectual disability v4.80 FOXP4 Achchuthan Shanmugasundram Publications for gene: FOXP4 were set to 33110267
Intellectual disability v4.79 FOXP4 Achchuthan Shanmugasundram reviewed gene: FOXP4: Rating: AMBER; Mode of pathogenicity: None; Publications: 33110267, 36301021, 36646976; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.79 FOXP4 Achchuthan Shanmugasundram Deleted their review
Intellectual disability v4.79 FOXP4 Achchuthan Shanmugasundram edited their review of gene: FOXP4: Changed publications to: 33110267, 36301021, 36646976
Intellectual disability v4.79 FOXP4 Achchuthan Shanmugasundram reviewed gene: FOXP4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: 33110267, 36301021, 36646976; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.79 PRRT2 Arina Puzriakova commented on gene: PRRT2
Intellectual disability v4.79 PRRT2 Arina Puzriakova Publications for gene: PRRT2 were set to 21937992; 23352743; 25595153; 23398397; 23126439
Intellectual disability v4.78 FOXRED1 Sarah Leigh Phenotypes for gene: FOXRED1 were changed from MITOCHONDRIAL COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 19, OMIM:618241; mitochondrial complex 1 deficiency, nuclear type 19, MONDO:0032624
Intellectual disability v4.77 GRIA2 Sarah Leigh Publications for gene: GRIA2 were set to 28725178; 26350204; 24896178; 22669415; 28630856; 31300657
Intellectual disability v4.76 GRIA2 Sarah Leigh Phenotypes for gene: GRIA2 were changed from Epileptic encephalopathy intellectual disability stereotypic hand movements; Neurodevelopmental disorder with language impairment and behavioral abnormalities MIM#618917 to Neurodevelopmental disorder with language impairment and behavioral abnormalities, OMIM:618917; neurodevelopmental disorder with language impairment and behavioral abnormalities, MONDO:0030060
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: ROBO1.
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram changed review comment from: Comment on gene classification: This gene should be rated green as this gene has been associated with intellectual disability from six unrelated cases. However, the MOI should be set as "BIALLELIC, autosomal or pseudoautosomal" as five of these cases were reported with biallelic variants and only one case was reported with monoallelic variant.

PMID:28286008 reported a boy with compound heterozygous variants that was presented with developmental delay in 13 months and had severe intellectual disability and hyperactivity at nine years of age. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia.

PMID:30692597 reported a five year old boy identified with a homozygous ROBO1 variant who had combined pituitary hormone deficiency, psychomotor developmental delay, severe intellectual disability, sensorineural hearing loss, strabismus and characteristic facial features.

PMID:35227688 reported eight patients including the boy reported in PMID:30692597. Of the other seven patients, three were presented with intellectual disability. Of these three patients, two harboured compound heterozygous and one harboured homozygous variants.

PMID:35348658 reported a patient identified with monoallelic de novo variant (p.D422G) who presented with early-onset epileptic encephalopathy and had severe developmental delay.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.; to: Comment on gene classification: This gene should be rated green as this gene has been associated with intellectual disability from six unrelated cases. However, the MOI should be set as "BIALLELIC, autosomal or pseudoautosomal" as five of these cases were reported with biallelic variants and only one case was reported with monoallelic variant.

PMID:28286008 reported a boy with compound heterozygous variants that was presented with developmental delay in 13 months and had severe intellectual disability and hyperactivity at nine years of age. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia.

PMID:30692597 reported a five year old boy identified with a homozygous ROBO1 variant who had combined pituitary hormone deficiency, psychomotor developmental delay, severe intellectual disability, sensorineural hearing loss, strabismus and characteristic facial features.

PMID:35227688 reported eight patients including the boy reported in PMID:30692597. Of the other seven patients, three were presented with intellectual disability. Of these three patients, two harboured compound heterozygous and one harboured homozygous variants.

PMID:35348658 reported a patient identified with monoallelic de novo variant (p.D422G) who presented with early-onset epileptic encephalopathy and had severe developmental delay.

This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.76 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.74 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.75 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD to ROBO1-related NDD; intellectual disability, MONDO:0001071
Intellectual disability v4.74 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.74 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.73 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.73 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.72 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Mode of inheritance for gene: ROBO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.71 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.70 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.70 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.70 ROBO1 Achchuthan Shanmugasundram Classified gene: ROBO1 as Amber List (moderate evidence)
Intellectual disability v4.70 ROBO1 Achchuthan Shanmugasundram Gene: robo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.69 ROBO1 Achchuthan Shanmugasundram reviewed gene: ROBO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28286008, 30692597, 35227688, 35348658; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 35271727
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 35271727
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 35271727
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 35271727
Intellectual disability v4.69 CHAMP1 Achchuthan Shanmugasundram Publications for gene: CHAMP1 were set to 0
Intellectual disability v4.68 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.68 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.68 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.68 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.67 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.67 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579 to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.67 CHAMP1 Achchuthan Shanmugasundram Phenotypes for gene: CHAMP1 were changed from INTELLECTUAL DISABILITY to Neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, OMIM:616579
Intellectual disability v4.66 HIST1H1E Achchuthan Shanmugasundram Publications for gene: HIST1H1E were set to 28475857
Intellectual disability v4.65 RAB39B Achchuthan Shanmugasundram Added comment: Comment on publications: Additional cases diagnosed with intellectual disability, autism, macrocephaly and poor motor coordination reported in PMIDs 29152164, 32873259 & 34761259. There are also ample functional evidence including studies from animal models described in these and other publications.
Intellectual disability v4.65 RAB39B Achchuthan Shanmugasundram Publications for gene: RAB39B were set to 20159109; 25434005; 11050621; 29152164; 32873259; 34761259
Intellectual disability v4.64 RAB39B Achchuthan Shanmugasundram Publications for gene: RAB39B were set to
Intellectual disability v4.63 RAB39B Achchuthan Shanmugasundram Phenotypes for gene: RAB39B were changed from Mental retardation, X-linked 72, 300271; Mental Retardation, X-linked; MENTAL RETARDATION X-LINKED TYPE 72 (MRX72) +/- PARKINSONS to Intellectual developmental disorder, X-linked 72, OMIM:300271; Waisman syndrome, OMIM:311510
Intellectual disability v4.62 TRPM3 Eleanor Williams Phenotypes for gene: TRPM3 were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures, OMIM:620224
Intellectual disability v4.61 TRPM3 Eleanor Williams Tag gene-checked was removed from gene: TRPM3.
Intellectual disability v4.61 TMEM63C Eleanor Williams Tag gene-checked tag was added to gene: TMEM63C.
Intellectual disability v4.61 SPATA5L1 Eleanor Williams Tag gene-checked tag was added to gene: SPATA5L1.
Intellectual disability v4.61 CCDC32 Eleanor Williams Tag gene-checked tag was added to gene: CCDC32.
Intellectual disability v4.61 WNK3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WNK3.
Intellectual disability v4.61 SRRM2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SRRM2.
Intellectual disability v4.61 SCAMP5 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SCAMP5.
Intellectual disability v4.61 SCAF4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SCAF4.
Intellectual disability v4.61 RAB11A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RAB11A.
Intellectual disability v4.61 HMGB1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HMGB1.
Intellectual disability v4.61 FOXP4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FOXP4.
Intellectual disability v4.61 DROSHA Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DROSHA.
Intellectual disability v4.61 CDK9 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CDK9.
Intellectual disability v4.61 BLOC1S1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: BLOC1S1.
Intellectual disability v4.61 ASCC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ASCC3.
Intellectual disability v4.61 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.61 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191 to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.60 PGM2L1 Achchuthan Shanmugasundram Phenotypes for gene: PGM2L1 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities, OMIM:620191
Intellectual disability v4.59 PGM2L1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: PGM2L1.
Intellectual disability v4.59 THUMPD1 Eleanor Williams Added comment: Comment on mode of inheritance: Adding the mode of inheritance of biallelic as this was missing. Autosomal recessive MOI in OMIM for a relevant phenotype.
Intellectual disability v4.59 THUMPD1 Eleanor Williams Mode of inheritance for gene: THUMPD1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.58 THUMPD1 Eleanor Williams Phenotypes for gene: THUMPD1 were changed from THUMPD1 neurodevelopment disorder to Neurodevelopmental disorder with speech delay and variable ocular anomalies, OMIM:619989
Intellectual disability v4.57 ISCA-37429-Loss Arina Puzriakova Phenotypes for Region: ISCA-37429-Loss were changed from Wolf-Hirschhorn syndrome, OMIM:194190 to Wolf-Hirschhorn syndrome, OMIM:194190
Intellectual disability v4.57 ISCA-37429-Loss Arina Puzriakova Phenotypes for Region: ISCA-37429-Loss were changed from 194190; Wolf-Hirschhorn syndrome to Wolf-Hirschhorn syndrome, OMIM:194190
Intellectual disability v4.56 ISCA-37420-Loss Arina Puzriakova Phenotypes for Region: ISCA-37420-Loss were changed from PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443 to Koolen-De Vries syndrome, OMIM:610443; Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature
Intellectual disability v4.55 ISCA-37420-Loss Arina Puzriakova commented on Region: ISCA-37420-Loss: Previously in phenotypes field:

PMID: 18628315 developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour, other clinically important features include epilepsy, heart defects and kidney/urologic anomalies; 610443; PMID: 25217958; Koolen-De Vries syndrome 610443
Intellectual disability v4.55 ISCA-37408-Loss Arina Puzriakova commented on Region: ISCA-37408-Loss
Intellectual disability v4.55 ISCA-37408-Loss Arina Puzriakova Phenotypes for Region: ISCA-37408-Loss were changed from PMID: 16963482 idiopathic intellectual disability including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies (multicystic kidney, hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features. Dysmorphic craniofacial features include progressive microcephaly, flat occiput, widened inner canthal distance, small palpebral fissures, ptosis, long and straight eyelashes, broad and high nasal root extending to a widened, prominent nasal tip with elongated, smooth philtrum, rounding of the upper vermillion border and everted lower lips. PMID: 18245392 A 32-year-old, mentally retarded male was referred to our centre for further clinical genetic analysis. He was born to non-consanguineous parents after 42 weeks gestation with a birth weight of 3500 g. He had a healthy older brother. In the neonatal period he was hypotonic and at 8 weeks of age he underwent surgery because of an inguinal hernia with removal of an atrophic right testis. His motor development was severely delayed with sitting at 3.5 years and walking at 5 years of age. Speech was poorly developed, characterised by the usage of only a few words. During infancy an optic nerve hypoplasia was diagnosed, and during childhood he frequently suffered from luxations of the patellae, which required surgery. At the age of 32 years his height is 163 cm (_3 SDS) and head circumference 52.5 cm (_2.5 SDS). He has a narrow receding forehead, widened inner canthal distance of 3.5 cm (90th centile), normal outer canthal distance of 8.5 cm (25th centile), telecanthus, short and down slanting palpebral fissures, epicanthal folds, ptosis, long, straight eyelashes, high nasal bridge, low set large ears, flat philtrum, small mouth with high, narrow palate and retrognathia. The thorax is broad with increased internipple distance and slight gynaecomastia. A recent renal ultrasound revealed multiple cysts in the left, dystrophic kidney and two uncomplicated cysts in the enlarged, right kidney. The patient has a normally sized phallus with absent right testis and small left testis. His hands show a simian crease right and tapering fingers with broad proximal interphalangeal joints. He shows sandal gaps on both flat feet with clinodactyly of the fourth and fifth toes (and more); 612513; PMID: 22579565 severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal cyst which has not been previously reported in other patients with this cytogenetic defect to Dysmorphic features, moderate to severe intellectual disability, microcephaly and renal anomalies
Intellectual disability v4.54 ISCA-46553-Loss Arina Puzriakova reviewed Region: ISCA-46553-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-46742-Loss Arina Puzriakova reviewed Region: ISCA-46742-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-46297-Loss Arina Puzriakova reviewed Region: ISCA-46297-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-37495-Loss Arina Puzriakova reviewed Region: ISCA-37495-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-46304-Gain Arina Puzriakova reviewed Region: ISCA-46304-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.54 ISCA-37423-Loss Arina Puzriakova edited their review of Region: ISCA-37423-Loss: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022).; Changed rating: GREEN
Intellectual disability v4.54 ISCA-37423-Gain Arina Puzriakova edited their review of Region: ISCA-37423-Gain: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates and triplosensitivity score (from 3 to 2) of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022). Regardless of the change in triplosensitivity score, it was deemed appropriate for this regions to remain green as evidence to support pathogenicity remains.; Changed rating: GREEN
Intellectual disability v4.54 ISCA-46553-Loss Arina Puzriakova Region: ISCA-46553-Loss was added
Region: ISCA-46553-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46553-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46553-Loss were set to 21204220; 15338008; 22067867; 21471554; 28503614
Intellectual disability v4.54 ISCA-46742-Loss Arina Puzriakova Region: ISCA-46742-Loss was added
Region: ISCA-46742-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46742-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46742-Loss were set to 27633570; 32562408; 29274487; 29220674
Intellectual disability v4.54 ISCA-46297-Loss Arina Puzriakova Region: ISCA-46297-Loss was added
Region: ISCA-46297-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46297-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-46297-Loss were set to 31204719; 19888295; 20301607; 25719193; 30836598
Intellectual disability v4.54 ISCA-37495-Loss Arina Puzriakova Region: ISCA-37495-Loss was added
Region: ISCA-37495-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-37495-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37495-Loss were set to 26227573
Intellectual disability v4.54 ISCA-46304-Gain Arina Puzriakova Region: ISCA-46304-Gain was added
Region: ISCA-46304-Gain was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46304-Gain 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 Region: ISCA-46304-Gain were set to 22679399; 29141583; 29618507; 32043567
Intellectual disability v4.54 ISCA-37423-Loss Arina Puzriakova GRCh38 position for ISCA-37423-Loss was changed from 8261773-11908210 to 8242542-11908820.
Intellectual disability v4.54 ISCA-37423-Gain Arina Puzriakova GRCh38 position for ISCA-37423-Gain was changed from 8261773-11908210 to 8242542-11908820.
Triplosensitivity Score for ISCA-37423-Gain was changed from 3 to 2.
Intellectual disability v4.53 CUX2 Arina Puzriakova Tag Q3_21_NHS_review was removed from gene: CUX2.
Intellectual disability v4.53 RAP1GDS1 Arina Puzriakova Tag Q3_22_rating was removed from gene: RAP1GDS1.
Tag Q3_22_expert_review was removed from gene: RAP1GDS1.
Intellectual disability v4.53 ZC4H2 Arina Puzriakova Tag Q4_21_MOI was removed from gene: ZC4H2.
Intellectual disability v4.53 PRODH Arina Puzriakova Tag Q2_22_rating was removed from gene: PRODH.
Tag Q2_22_expert_review was removed from gene: PRODH.
Tag Q2_22_NHS_review was removed from gene: PRODH.
Intellectual disability v4.53 ZBTB7A Arina Puzriakova Tag Q2_22_rating was removed from gene: ZBTB7A.
Tag Q2_22_NHS_review was removed from gene: ZBTB7A.
Intellectual disability v4.53 THUMPD1 Arina Puzriakova Tag Q2_22_rating was removed from gene: THUMPD1.
Tag Q2_22_NHS_review was removed from gene: THUMPD1.
Intellectual disability v4.53 SRRM2 Arina Puzriakova Tag Q2_22_rating was removed from gene: SRRM2.
Intellectual disability v4.53 SPRED2 Arina Puzriakova Tag Q1_22_rating was removed from gene: SPRED2.
Intellectual disability v4.53 SPATA5L1 Arina Puzriakova Tag Q1_22_rating was removed from gene: SPATA5L1.
Intellectual disability v4.53 SNORD118 Arina Puzriakova Tag Q2_22_rating was removed from gene: SNORD118.
Tag Q2_22_NHS_review was removed from gene: SNORD118.
Intellectual disability v4.53 SLC12A5 Arina Puzriakova Tag Q1_22_MOI was removed from gene: SLC12A5.
Intellectual disability v4.53 SCAF4 Arina Puzriakova Tag Q2_22_rating was removed from gene: SCAF4.
Tag Q2_22_NHS_review was removed from gene: SCAF4.
Intellectual disability v4.53 PRPF8 Arina Puzriakova Tag Q2_22_rating was removed from gene: PRPF8.
Intellectual disability v4.53 PHF14 Arina Puzriakova Tag Q2_22_rating was removed from gene: PHF14.
Intellectual disability v4.53 PEX6 Arina Puzriakova Tag Q1_22_MOI was removed from gene: PEX6.
Intellectual disability v4.53 NAPB Arina Puzriakova Tag Q2_22_rating was removed from gene: NAPB.
Tag Q2_22_NHS_review was removed from gene: NAPB.
Intellectual disability v4.53 MED13 Arina Puzriakova Tag Q2_22_rating was removed from gene: MED13.
Tag Q2_22_NHS_review was removed from gene: MED13.
Intellectual disability v4.53 KDM5C Arina Puzriakova Tag Q3_21_MOI was removed from gene: KDM5C.
Intellectual disability v4.53 HSPD1 Arina Puzriakova Tag Q2_22_MOI was removed from gene: HSPD1.
Intellectual disability v4.53 DTYMK Arina Puzriakova Tag Q2_22_rating was removed from gene: DTYMK.
Intellectual disability v4.53 DROSHA Arina Puzriakova Tag Q2_22_rating was removed from gene: DROSHA.
Intellectual disability v4.53 DHDDS Arina Puzriakova Tag Q4_21_MOI was removed from gene: DHDDS.
Intellectual disability v4.53 COG5 Arina Puzriakova Tag Q3_21_MOI was removed from gene: COG5.
Intellectual disability v4.53 CELF2 Arina Puzriakova Tag Q2_22_rating was removed from gene: CELF2.
Tag Q2_22_NHS_review was removed from gene: CELF2.
Intellectual disability v4.53 CACNA2D1 Arina Puzriakova Tag Q2_22_rating was removed from gene: CACNA2D1.
Intellectual disability v4.53 BSCL2 Arina Puzriakova Tag Q3_21_MOI was removed from gene: BSCL2.
Intellectual disability v4.53 ARHGEF9 Arina Puzriakova Tag Q3_21_MOI was removed from gene: ARHGEF9.
Intellectual disability v4.53 AP1S2 Arina Puzriakova Tag Q4_21_MOI was removed from gene: AP1S2.
Intellectual disability v4.53 AFF3 Arina Puzriakova Tag for-review was removed from gene: AFF3.
Intellectual disability v4.53 ACO2 Arina Puzriakova Tag Q2_22_MOI was removed from gene: ACO2.
Intellectual disability v4.53 ACER3 Arina Puzriakova Tag Q1_22_rating was removed from gene: ACER3.
Intellectual disability v4.53 ZMYM2 Arina Puzriakova Tag Q3_22_rating was removed from gene: ZMYM2.
Tag Q3_22_NHS_review was removed from gene: ZMYM2.
Intellectual disability v4.53 WNK3 Arina Puzriakova Tag Q3_22_rating was removed from gene: WNK3.
Intellectual disability v4.53 TPP2 Arina Puzriakova Tag Q3_22_rating was removed from gene: TPP2.
Intellectual disability v4.53 TMEM63C Arina Puzriakova Tag Q3_22_rating was removed from gene: TMEM63C.
Intellectual disability v4.53 TIAM1 Arina Puzriakova Tag Q3_22_rating was removed from gene: TIAM1.
Tag Q3_22_MOI was removed from gene: TIAM1.
Intellectual disability v4.53 TAF8 Arina Puzriakova Tag Q3_22_rating was removed from gene: TAF8.
Tag Q3_22_NHS_review was removed from gene: TAF8.
Intellectual disability v4.53 STT3A Arina Puzriakova Tag Q3_22_MOI was removed from gene: STT3A.
Tag Q3_22_NHS_review was removed from gene: STT3A.
Intellectual disability v4.53 SLC38A3 Arina Puzriakova Tag Q3_22_rating was removed from gene: SLC38A3.
Intellectual disability v4.53 SCAMP5 Arina Puzriakova Tag Q3_22_rating was removed from gene: SCAMP5.
Intellectual disability v4.53 RAB11A Arina Puzriakova Tag watchlist was removed from gene: RAB11A.
Tag Q3_22_rating was removed from gene: RAB11A.
Intellectual disability v4.53 PRDM13 Arina Puzriakova Tag Q3_22_rating was removed from gene: PRDM13.
Intellectual disability v4.53 POLRMT Arina Puzriakova Tag Q3_22_rating was removed from gene: POLRMT.
Intellectual disability v4.53 PDZD8 Arina Puzriakova Tag Q3_22_rating was removed from gene: PDZD8.
Intellectual disability v4.53 OGDHL Arina Puzriakova Tag Q3_22_rating was removed from gene: OGDHL.
Intellectual disability v4.53 NSRP1 Arina Puzriakova Tag Q3_22_rating was removed from gene: NSRP1.
Intellectual disability v4.53 NRCAM Arina Puzriakova Tag Q3_22_rating was removed from gene: NRCAM.
Intellectual disability v4.53 HMGB1 Arina Puzriakova Tag Q3_22_rating was removed from gene: HMGB1.
Intellectual disability v4.53 HK1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: HK1.
Tag Q3_22_NHS_review was removed from gene: HK1.
Intellectual disability v4.53 GLRA2 Arina Puzriakova Tag Q3_22_rating was removed from gene: GLRA2.
Intellectual disability v4.53 FBXW7 Arina Puzriakova Tag Q3_22_rating was removed from gene: FBXW7.
Tag Q3_22_MOI was removed from gene: FBXW7.
Intellectual disability v4.53 FBXO28 Arina Puzriakova Tag Q3_22_rating was removed from gene: FBXO28.
Tag Q3_22_MOI was removed from gene: FBXO28.
Intellectual disability v4.53 EMC1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: EMC1.
Intellectual disability v4.53 EDEM3 Arina Puzriakova Tag Q3_22_rating was removed from gene: EDEM3.
Intellectual disability v4.53 DOCK8 Arina Puzriakova Tag Q3_22_rating was removed from gene: DOCK8.
Tag Q3_22_MOI was removed from gene: DOCK8.
Tag Q3_22_NHS_review was removed from gene: DOCK8.
Tag Q3_22_expert_review was removed from gene: DOCK8.
Intellectual disability v4.53 CUL3 Arina Puzriakova Tag Q3_22_rating was removed from gene: CUL3.
Tag Q3_22_NHS_review was removed from gene: CUL3.
Intellectual disability v4.53 CHKA Arina Puzriakova Tag Q3_22_rating was removed from gene: CHKA.
Intellectual disability v4.53 CCDC32 Arina Puzriakova Tag watchlist was removed from gene: CCDC32.
Tag Q3_22_rating was removed from gene: CCDC32.
Intellectual disability v4.53 CACNA1A Arina Puzriakova Tag Q3_22_MOI was removed from gene: CACNA1A.
Intellectual disability v4.53 BLOC1S1 Arina Puzriakova Tag Q3_22_rating was removed from gene: BLOC1S1.
Intellectual disability v4.53 ATP6V0A1 Arina Puzriakova Tag Q3_22_rating was removed from gene: ATP6V0A1.
Tag Q3_22_NHS_review was removed from gene: ATP6V0A1.
Intellectual disability v4.53 ATP2B1 Arina Puzriakova Tag Q3_22_rating was removed from gene: ATP2B1.
Intellectual disability v4.53 ATG7 Arina Puzriakova Tag Q3_22_rating was removed from gene: ATG7.
Intellectual disability v4.53 ANK3 Arina Puzriakova Tag Q3_22_rating was removed from gene: ANK3.
Tag Q3_22_MOI was removed from gene: ANK3.
Tag Q3_22_NHS_review was removed from gene: ANK3.
Intellectual disability v4.53 ALKBH8 Arina Puzriakova Tag Q3_22_rating was removed from gene: ALKBH8.
Intellectual disability v4.53 ADD1 Arina Puzriakova Tag Q3_22_rating was removed from gene: ADD1.
Intellectual disability v4.53 PHF14 Arina Puzriakova reviewed gene: PHF14: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 DROSHA Arina Puzriakova reviewed gene: DROSHA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 RAP1GDS1 Arina Puzriakova edited their review of gene: RAP1GDS1: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.; Changed rating: AMBER
Intellectual disability v4.53 PRODH Arina Puzriakova reviewed gene: PRODH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 ZC4H2 Arina Puzriakova commented on gene: ZC4H2
Intellectual disability v4.53 ZBTB7A Arina Puzriakova reviewed gene: ZBTB7A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 THUMPD1 Arina Puzriakova reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SRRM2 Arina Puzriakova reviewed gene: SRRM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SPRED2 Arina Puzriakova reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SPATA5L1 Arina Puzriakova reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SNORD118 Arina Puzriakova reviewed gene: SNORD118: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SLC12A5 Arina Puzriakova commented on gene: SLC12A5
Intellectual disability v4.53 SCAF4 Arina Puzriakova edited their review of gene: SCAF4: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 PRPF8 Arina Puzriakova reviewed gene: PRPF8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 PEX6 Arina Puzriakova commented on gene: PEX6
Intellectual disability v4.53 NAPB Arina Puzriakova edited their review of gene: NAPB: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 MED13 Arina Puzriakova reviewed gene: MED13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 KDM5C Arina Puzriakova commented on gene: KDM5C: The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 HSPD1 Arina Puzriakova commented on gene: HSPD1: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 DTYMK Arina Puzriakova reviewed gene: DTYMK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 DHDDS Arina Puzriakova commented on gene: DHDDS: The mode of inheritance of this gene has been updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 COG5 Arina Puzriakova commented on gene: COG5
Intellectual disability v4.53 CELF2 Arina Puzriakova edited their review of gene: CELF2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 CACNA2D1 Arina Puzriakova reviewed gene: CACNA2D1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 BSCL2 Arina Puzriakova commented on gene: BSCL2: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 ARHGEF9 Arina Puzriakova commented on gene: ARHGEF9: The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 AP1S2 Arina Puzriakova commented on gene: AP1S2: The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 AFF3 Arina Puzriakova edited their review of gene: AFF3: Added comment: The rating of this gene has been updated to Green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 ACO2 Arina Puzriakova commented on gene: ACO2
Intellectual disability v4.53 ACER3 Arina Puzriakova commented on gene: ACER3: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 ZMYM2 Arina Puzriakova reviewed gene: ZMYM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 WNK3 Arina Puzriakova commented on gene: WNK3: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 TPP2 Arina Puzriakova reviewed gene: TPP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 TMEM63C Arina Puzriakova reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 TIAM1 Arina Puzriakova reviewed gene: TIAM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 TAF8 Arina Puzriakova edited their review of gene: TAF8: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 STT3A Arina Puzriakova commented on gene: STT3A: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 SLC38A3 Arina Puzriakova reviewed gene: SLC38A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SCAMP5 Arina Puzriakova reviewed gene: SCAMP5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 RAB11A Arina Puzriakova reviewed gene: RAB11A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 PRDM13 Arina Puzriakova reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 POLRMT Arina Puzriakova edited their review of gene: POLRMT: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 PDZD8 Arina Puzriakova reviewed gene: PDZD8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 OGDHL Arina Puzriakova edited their review of gene: OGDHL: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 NSRP1 Arina Puzriakova edited their review of gene: NSRP1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 NRCAM Arina Puzriakova reviewed gene: NRCAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 HMGB1 Arina Puzriakova edited their review of gene: HMGB1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 HK1 Arina Puzriakova commented on gene: HK1
Intellectual disability v4.53 GLRA2 Arina Puzriakova reviewed gene: GLRA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 FBXW7 Arina Puzriakova reviewed gene: FBXW7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 FBXO28 Arina Puzriakova reviewed gene: FBXO28: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 EMC1 Arina Puzriakova commented on gene: EMC1
Intellectual disability v4.53 EDEM3 Arina Puzriakova edited their review of gene: EDEM3: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 DOCK8 Arina Puzriakova reviewed gene: DOCK8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 CUL3 Arina Puzriakova edited their review of gene: CUL3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 CHKA Arina Puzriakova reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 CCDC32 Arina Puzriakova reviewed gene: CCDC32: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 CACNA1A Arina Puzriakova commented on gene: CACNA1A
Intellectual disability v4.53 BLOC1S1 Arina Puzriakova edited their review of gene: BLOC1S1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 ATP6V0A1 Arina Puzriakova reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 ATP2B1 Arina Puzriakova reviewed gene: ATP2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 ATG7 Arina Puzriakova edited their review of gene: ATG7: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 ANK3 Arina Puzriakova reviewed gene: ANK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 ALKBH8 Arina Puzriakova commented on gene: ALKBH8: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 ADD1 Arina Puzriakova reviewed gene: ADD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.52 ZMYM2 Arina Puzriakova Source NHS GMS was added to ZMYM2.
Source Expert Review Green was added to ZMYM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ZC4H2 Arina Puzriakova Source NHS GMS was added to ZC4H2.
Mode of inheritance for gene ZC4H2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 ZBTB7A Arina Puzriakova Source NHS GMS was added to ZBTB7A.
Source Expert Review Green was added to ZBTB7A.
Mode of inheritance for gene ZBTB7A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 WNK3 Arina Puzriakova Source NHS GMS was added to WNK3.
Source Expert Review Green was added to WNK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TPP2 Arina Puzriakova Source NHS GMS was added to TPP2.
Source Expert Review Green was added to TPP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TMEM63C Arina Puzriakova Source NHS GMS was added to TMEM63C.
Source Expert Review Green was added to TMEM63C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TIAM1 Arina Puzriakova Source NHS GMS was added to TIAM1.
Source Expert Review Green was added to TIAM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 THUMPD1 Arina Puzriakova Source NHS GMS was added to THUMPD1.
Source Expert Review Green was added to THUMPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TAF8 Arina Puzriakova Source NHS GMS was added to TAF8.
Source Expert Review Green was added to TAF8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 STT3A Arina Puzriakova Source NHS GMS was added to STT3A.
Mode of inheritance for gene STT3A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 SRRM2 Arina Puzriakova Source NHS GMS was added to SRRM2.
Source Expert Review Green was added to SRRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SPRED2 Arina Puzriakova Source NHS GMS was added to SPRED2.
Source Expert Review Green was added to SPRED2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SPATA5L1 Arina Puzriakova Source NHS GMS was added to SPATA5L1.
Source Expert Review Green was added to SPATA5L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SNORD118 Arina Puzriakova Source NHS GMS was added to SNORD118.
Source Expert Review Green was added to SNORD118.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SLC38A3 Arina Puzriakova Source NHS GMS was added to SLC38A3.
Source Expert Review Green was added to SLC38A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SLC12A5 Arina Puzriakova Source NHS GMS was added to SLC12A5.
Mode of inheritance for gene SLC12A5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 SCAMP5 Arina Puzriakova Source Expert Review Green was added to SCAMP5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SCAF4 Arina Puzriakova Source NHS GMS was added to SCAF4.
Source Expert Review Green was added to SCAF4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 RAB11A Arina Puzriakova Source NHS GMS was added to RAB11A.
Source Expert Review Green was added to RAB11A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PRPF8 Arina Puzriakova Source NHS GMS was added to PRPF8.
Source Expert Review Green was added to PRPF8.
Mode of inheritance for gene PRPF8 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PRODH Arina Puzriakova Source Expert Review Amber was added to PRODH.
Source NHS GMS was added to PRODH.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v4.52 PRDM13 Arina Puzriakova Source NHS GMS was added to PRDM13.
Source Expert Review Green was added to PRDM13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 POLRMT Arina Puzriakova Source Expert Review Green was added to POLRMT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PHF14 Arina Puzriakova Source NHS GMS was added to PHF14.
Intellectual disability v4.52 PEX6 Arina Puzriakova Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 PDZD8 Arina Puzriakova Source NHS GMS was added to PDZD8.
Source Expert Review Green was added to PDZD8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 OGDHL Arina Puzriakova Source NHS GMS was added to OGDHL.
Source Expert Review Green was added to OGDHL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 NSRP1 Arina Puzriakova Source NHS GMS was added to NSRP1.
Source Expert Review Green was added to NSRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 NRCAM Arina Puzriakova Source NHS GMS was added to NRCAM.
Source Expert Review Green was added to NRCAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 NAPB Arina Puzriakova Source Expert Review Green was added to NAPB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 MED13 Arina Puzriakova Source NHS GMS was added to MED13.
Source Expert Review Green was added to MED13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 KDM5C Arina Puzriakova Source NHS GMS was added to KDM5C.
Mode of inheritance for gene KDM5C was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 HSPD1 Arina Puzriakova Source NHS GMS was added to HSPD1.
Mode of inheritance for gene HSPD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 HMGB1 Arina Puzriakova Source NHS GMS was added to HMGB1.
Source Expert Review Green was added to HMGB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 HK1 Arina Puzriakova Source NHS GMS was added to HK1.
Mode of inheritance for gene HK1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.52 GLRA2 Arina Puzriakova Source NHS GMS was added to GLRA2.
Source Expert Review Green was added to GLRA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 FBXW7 Arina Puzriakova Source NHS GMS was added to FBXW7.
Source Expert Review Green was added to FBXW7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 FBXO28 Arina Puzriakova Source NHS GMS was added to FBXO28.
Source Expert Review Green was added to FBXO28.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 EMC1 Arina Puzriakova Source NHS GMS was added to EMC1.
Mode of inheritance for gene EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 EDEM3 Arina Puzriakova Source NHS GMS was added to EDEM3.
Source Expert Review Green was added to EDEM3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 DTYMK Arina Puzriakova Source NHS GMS was added to DTYMK.
Source Expert Review Green was added to DTYMK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 DROSHA Arina Puzriakova Source NHS GMS was added to DROSHA.
Intellectual disability v4.52 DOCK8 Arina Puzriakova Source Expert Review Amber was added to DOCK8.
Source NHS GMS was added to DOCK8.
Mode of inheritance for gene DOCK8 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v4.52 DHDDS Arina Puzriakova Source NHS GMS was added to DHDDS.
Mode of inheritance for gene DHDDS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.52 CUL3 Arina Puzriakova Source NHS GMS was added to CUL3.
Source Expert Review Green was added to CUL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 COG5 Arina Puzriakova Source NHS GMS was added to COG5.
Mode of inheritance for gene COG5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 CHKA Arina Puzriakova Source NHS GMS was added to CHKA.
Source Expert Review Green was added to CHKA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CELF2 Arina Puzriakova Source NHS GMS was added to CELF2.
Source Expert Review Green was added to CELF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CCDC32 Arina Puzriakova Source NHS GMS was added to CCDC32.
Source Expert Review Green was added to CCDC32.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CACNA2D1 Arina Puzriakova Source NHS GMS was added to CACNA2D1.
Source Expert Review Green was added to CACNA2D1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CACNA1A Arina Puzriakova Source NHS GMS was added to CACNA1A.
Mode of inheritance for gene CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 BSCL2 Arina Puzriakova Source NHS GMS was added to BSCL2.
Mode of inheritance for gene BSCL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 BLOC1S1 Arina Puzriakova Source NHS GMS was added to BLOC1S1.
Source Expert Review Green was added to BLOC1S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATP6V0A1 Arina Puzriakova Source NHS GMS was added to ATP6V0A1.
Source Expert Review Green was added to ATP6V0A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATP2B1 Arina Puzriakova Source NHS GMS was added to ATP2B1.
Source Expert Review Green was added to ATP2B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATG7 Arina Puzriakova Source NHS GMS was added to ATG7.
Source Expert Review Green was added to ATG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ARHGEF9 Arina Puzriakova Source NHS GMS was added to ARHGEF9.
Mode of inheritance for gene ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 AP1S2 Arina Puzriakova Source NHS GMS was added to AP1S2.
Mode of inheritance for gene AP1S2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 ANK3 Arina Puzriakova Source NHS GMS was added to ANK3.
Source Expert Review Green was added to ANK3.
Mode of inheritance for gene ANK3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ALKBH8 Arina Puzriakova Source NHS GMS was added to ALKBH8.
Source Expert Review Green was added to ALKBH8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 AFF3 Arina Puzriakova Source NHS GMS was added to AFF3.
Source Expert Review Green was added to AFF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ADD1 Arina Puzriakova Source NHS GMS was added to ADD1.
Source Expert Review Green was added to ADD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ACO2 Arina Puzriakova Source NHS GMS was added to ACO2.
Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 ACER3 Arina Puzriakova Source NHS GMS was added to ACER3.
Source Expert Review Green was added to ACER3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.51 KDM2B Mike Spiller gene: KDM2B was added
gene: KDM2B was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM2B were set to PMID: 36322151; 35128353; 35710456
Review for gene: KDM2B was set to GREEN
Added comment: van Jaarsveld et al 2022 PMID: 36322151

Majority of variants are missense, strong evidence for hotspot in CXXC domain.(7 different de Novo missenses + 1 de Novo in frame del. Same inframe del also found de novo in NHS GMS patient. All absent from gnomAD, region highly constrained).

Also 3 LOF SNVs and 3 patients with deletions including this gene, although not all are de novo and most also have potential alternate causes.

All have developmental delay. Almost all have intellectual disability ranging from mild to moderate, speech delay common..7 with cardiac abnormalities, 4 with kidney abnormalities.

Also 2 variants published in this region in PMID: 35710456, 35904121.

KDM2B methylation episignature recorded. CXXC variants show strong clustering, highly distinct from control dataset. LOF variants (including dels) also reported to show distinct episignature from controls, and from CXXC variants. While the data supports a KDM2B LOF episignature, this is not as clear, and may not be as specific, as the CXXC signature.

Mouse model also supports importance of CXXC domain, with mice heterozygous for CXXC-deleted KDM2B showing neurological defects (PMID: 35128353).

Evidence very strong for CXXC missenses less clear for haploinsufficiency.

Overall sufficient evidence from cases and episignature evidence to include as green for ID.
Sources: Literature
Intellectual disability v4.51 ZMYM3 Sarah Leigh edited their review of gene: ZMYM3: Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. Using the MatchMaker Exchange, PMID: 36586412 reports 23 ZMYM3 variants in 27 individuals (24 males, 3 females) with a neurodevelopmental delay phenotype. Of those assessed 17/20 had intellectual disability, there were other features that overlapped between the individuals including speech delay, motor delay, ASD traits, behavioral problems, facial dys-morphism, microcephaly, short stature.; Changed rating: GREEN; Changed publications to: 36586412; Changed phenotypes to: neurodevelopmental delay
Intellectual disability v4.51 ZMYM3 Sarah Leigh Classified gene: ZMYM3 as Amber List (moderate evidence)
Intellectual disability v4.51 ZMYM3 Sarah Leigh Gene: zmym3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.50 ZMYM3 Sarah Leigh Classified gene: ZMYM3 as Red List (low evidence)
Intellectual disability v4.50 ZMYM3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.50 ZMYM3 Sarah Leigh Gene: zmym3 has been classified as Red List (Low Evidence).
Intellectual disability v4.49 ZMYM3 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: ZMYM3.
Intellectual disability v4.49 ZMYM3 Sarah Leigh Publications for gene: ZMYM3 were set to 26350204; 24721225; 8817323
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.47 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.47 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Intellectual disability; short stature; autism spectrum disorder to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.46 BAP1 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: BAP1.
Intellectual disability v4.46 BAP1 Mafalda Gomes commented on gene: BAP1: Kry et al. (2022) performed trio-WES in a cohort with a rare syndromic NDD and identified de novo missense variants in 11 unrelated individuals. All individuals had DD or ID characterised notably by speech (11/11) and motor delay (6/11). Additional common characteristics were hypotonia, (7/11), seizures (6/11), and abnormal behaviour (8/10), including ASD, ADHD, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations involving the hands, feet, or spine. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In summary, this gene should be promoted to GREEN in this panel, with autosomal dominant mode of inheritance.
Intellectual disability v4.45 BAP1 Mafalda Gomes Source Expert Review Amber was added to BAP1.
Mode of inheritance for gene BAP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Amber List (moderate evidence)
Intellectual disability v4.44 TMEM147 Sarah Leigh Classified gene: TMEM147 as Amber List (moderate evidence)
Intellectual disability v4.44 TMEM147 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.44 TMEM147 Sarah Leigh Gene: tmem147 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.43 TMEM147 Sarah Leigh gene: TMEM147 was added
gene: TMEM147 was added to Intellectual disability. Sources: Literature
Q1_23_promote_green tags were added to gene: TMEM147.
Mode of inheritance for gene: TMEM147 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM147 were set to 36044892
Phenotypes for gene: TMEM147 were set to Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly, OMIM:620075
Review for gene: TMEM147 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. PMID: 36044892 reports 12 variants in at least 15 unrelated derived from GeneMatcher. Supportive functional evidence is also presented.
Sources: Literature
Intellectual disability v4.42 PAN2 Sarah Leigh edited their review of gene: PAN2: Added comment: PAN2 is not associated with a phenotype in OMIM, but has a moderate association with PAN2-related neurodevelopmental disorder with multiple congenital anomalies in Gen2Phen. PMID: 29620724 reports one homozygous variant in one case and PMID: 35304602 reports a further three homozygous variants in three unrelated cases. It would appear that the syndrome associated with PAN2 variants has multiple congenital anomalies (PMID: 35304602, table 1), including intellectual disabilty ranging from mild to global developmental delay.; Changed rating: GREEN
Intellectual disability v4.42 PAN2 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: PAN2.
Intellectual disability v4.42 PAN2 Sarah Leigh Classified gene: PAN2 as Amber List (moderate evidence)
Intellectual disability v4.42 PAN2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.42 PAN2 Sarah Leigh Gene: pan2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.41 PAN2 Sarah Leigh Publications for gene: PAN2 were set to 29620724; https://doi.org/10.1038/s41431-022-01077-y
Intellectual disability v4.40 HIST1H4D Sarah Leigh commented on gene: HIST1H4D: HIST1H4D is the previous symbol for H4 clustered histone 4 with the approved symbol: H4C4 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4782).
Intellectual disability v4.40 HIST1H4D Sarah Leigh Classified gene: HIST1H4D as Red List (low evidence)
Intellectual disability v4.40 HIST1H4D Sarah Leigh Gene: hist1h4d has been classified as Red List (Low Evidence).
Intellectual disability v4.39 HIST1H4D Sarah Leigh Tag new-gene-name tag was added to gene: HIST1H4D.
Intellectual disability v4.39 HIST1H4D Sarah Leigh reviewed gene: HIST1H4D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.39 HIST1H4F Sarah Leigh Classified gene: HIST1H4F as Red List (low evidence)
Intellectual disability v4.39 HIST1H4F Sarah Leigh Gene: hist1h4f has been classified as Red List (Low Evidence).
Intellectual disability v4.38 HIST1H4F Sarah Leigh edited their review of gene: HIST1H4F: Added comment: H4C6 is not associated with a phenotype in OMIM or Gen2Phen. PMID: 35202563 reports single H4C6 variant in a case with a neurodevelopmental syndrome, based on functional studies, the authors suggest that the variant does not have a loss of function action.; Changed rating: RED
Intellectual disability v4.38 HIST1H4F Sarah Leigh commented on gene: HIST1H4F
Intellectual disability v4.38 HIST1H4F Sarah Leigh Tag new-gene-name tag was added to gene: HIST1H4F.
Intellectual disability v4.38 HIST1H4I Sarah Leigh commented on gene: HIST1H4I: Associated with Tessadori-van Haaften neurodevelopmental syndrome 4, (OMIM:619951), but not with a phenotype in Gen2Phen. PMID: 35202563 reports two H4C9 variants in two patients with a neurodevelopmental syndrome, based on functional studies, the authors suggest that the variants do not have a loss of function action.
Intellectual disability v4.38 HIST1H4I Sarah Leigh Classified gene: HIST1H4I as Amber List (moderate evidence)
Intellectual disability v4.38 HIST1H4I Sarah Leigh Gene: hist1h4i has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.37 HIST1H4I Sarah Leigh Phenotypes for gene: HIST1H4I were changed from Global developmental delay; Intellectual disability; Microcephaly; Growth abnormality; Abnormality of the face to Tessadori-van Haaften neurodevelopmental syndrome 4, OMIM:619951; Tessadori-Van Haaften neurodevelopmental syndrome 4, MONDO:0031000
Intellectual disability v4.36 HIST1H4I Sarah Leigh commented on gene: HIST1H4I
Intellectual disability v4.36 HIST1H4I Sarah Leigh Tag new-gene-name tag was added to gene: HIST1H4I.
Intellectual disability v4.36 HIST1H4E Sarah Leigh Tag Q1_23_promote_green tag was added to gene: HIST1H4E.
Intellectual disability v4.36 HIST1H4E Sarah Leigh edited their review of gene: HIST1H4E: Added comment: Associated with in Tessadori-van Haaften neurodevelopmental syndrome 3 (OMIM:619950), but not with a phenotype in Gen2Phen. PMID: 35202563 reports seven H4C5 variants in 17 patients with a neurodevelopmental syndrome, based on functional studies, the authors suggest that the variants do not have a loss of function action.; Changed rating: GREEN
Intellectual disability v4.36 HIST1H4E Sarah Leigh Classified gene: HIST1H4E as Amber List (moderate evidence)
Intellectual disability v4.36 HIST1H4E Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.36 HIST1H4E Sarah Leigh Gene: hist1h4e has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.35 HIST1H4E Sarah Leigh commented on gene: HIST1H4E
Intellectual disability v4.35 HIST1H4E Sarah Leigh Tag new-gene-name tag was added to gene: HIST1H4E.
Intellectual disability v4.35 HIST1H4E Sarah Leigh Phenotypes for gene: HIST1H4E were changed from Global developmental delay; Intellectual disability; Microcephaly; Growth abnormality; Abnormality of the face to Tessadori-van Haaften neurodevelopmental syndrome 3, OMIM:619950; Tessadori-Van Haaften neurodevelopmental syndrome 3 MONDO:0030993
Intellectual disability v4.34 ZNF292 Sarah Leigh edited their review of gene: ZNF292: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least seven autosomal dominant or de novo ZNF292 variants have been reported in at least eleven unrelated cases of Intellectual developmental disorder, autosomal dominant 64 (OMIM: 619188)(PMID: 31723249).; Changed rating: GREEN
Intellectual disability v4.34 ZNF292 Sarah Leigh Classified gene: ZNF292 as Amber List (moderate evidence)
Intellectual disability v4.34 ZNF292 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.34 ZNF292 Sarah Leigh Gene: znf292 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.33 ZNF292 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: ZNF292.
Tag Q1_23_NHS_review tag was added to gene: ZNF292.
Intellectual disability v4.33 ZNF292 Sarah Leigh Phenotypes for gene: ZNF292 were changed from Intellectual disability; Autism; Attention deficit hyperactivity disorder; Abnormality of the face; Abnormal muscle tone; Abnormality of nervous system morphology; Growth abnormality; Feeding difficulties; Abnormality of the skeletal system; Abnormality of the cardiovascular system; Microcephaly; Seizures to Intellectual developmental disorder, autosomal dominant 64, OMIM:619188; intellectual developmental disorder, autosomal dominant 64, MONDO:0030934
Intellectual disability v4.32 PAX6 Sarah Leigh Tag Q1_23_demote_red tag was added to gene: PAX6.
Tag Q1_23_NHS_review tag was added to gene: PAX6.
Intellectual disability v4.32 PAX6 Sarah Leigh reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.32 ZNF292 Ian Berry reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31723249; Phenotypes: Intellectual disability, mild, ASD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v4.32 KDM6A Arina Puzriakova Phenotypes for gene: KDM6A were changed from Kabuki syndrome 2, 300867; Kabuki syndrome; KABUKI SYNDROME 2; KABUK2 to Kabuki syndrome 2, OMIM:300867
Intellectual disability v4.31 STAT5B Arina Puzriakova Mode of inheritance for gene: STAT5B was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability v4.30 STAT5B Arina Puzriakova Phenotypes for gene: STAT5B were changed from to Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, OMIM:245590; Growth hormone insensitivity with immune dysregulation 2, autosomal dominant, OMIM:618985
Intellectual disability v4.29 GHR Arina Puzriakova Phenotypes for gene: GHR were changed from Laron dwarfism, 262500; Short stature, 604271; {Hypercholesterolemia, familial, modifier of}, 143890; Increased responsiveness to growth hormone to Laron dwarfism, OMIM:262500; Growth hormone insensitivity, partial, OMIM:604271; Increased responsiveness to growth hormone, OMIM:604271
Intellectual disability v4.28 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from Polymicrogyria, symmetric or asymmetric, 610031; POLYMICROGYRIA ASYMMETRIC (PMGA) to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Intellectual disability v4.27 TBC1D7 Arina Puzriakova Phenotypes for gene: TBC1D7 were changed from intellectual disability; macrocephaly; megalencephaly to Macrocephaly/megalencephaly syndrome, autosomal recessive, OMIM:248000
Intellectual disability v4.26 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from PAFAH1B1-Associated Lissencephaly/Subcortical Band Heterotopia; LISSENCEPHALY TYPE 1 (LIS1) to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Intellectual disability v4.25 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Lissencephaly, X-linked, 300067Subcortical laminal heteropia, X-linked, 300067; SUBCORTICAL BAND HETEROTOPIA X-LINKED (SBHX) to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Intellectual disability v4.24 DDX3X Arina Puzriakova Phenotypes for gene: DDX3X were changed from Intellectual disability, Mental retardation, X-linked 102, 300958 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958
Intellectual disability v4.23 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Leigh syndrome due to cytochrome c oxidase deficiency, 256000Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119; MITOCHONDRIAL COMPLEX IV DEFICIENCY (MT-C4D) to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Intellectual disability v4.22 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from LEIGH SYNDROME (LS) to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Intellectual disability v4.21 SOX4 Arina Puzriakova Phenotypes for gene: SOX4 were changed from Coffin-Siris syndrome 10, 618506; Syndromic intellectual disability; Global developmental delay; Intellectual disability; Growth delay; Clinodactyly of the 5th finger; facial dysmorphism to Coffin-Siris syndrome 10, OMIM:618506; Syndromic intellectual disability; Global developmental delay; Intellectual disability; Growth delay; Clinodactyly of the 5th finger; facial dysmorphism
Intellectual disability v4.20 SOX4 Arina Puzriakova Publications for gene: SOX4 were set to 30661772
Intellectual disability v4.19 CASK Arina Puzriakova Publications for gene: CASK were set to
Intellectual disability v4.18 KLHL20 Arina Puzriakova Tag Q4_22_promote_green tag was added to gene: KLHL20.
Intellectual disability v4.18 KLHL20 Arina Puzriakova Classified gene: KLHL20 as Amber List (moderate evidence)
Intellectual disability v4.18 KLHL20 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel review.
-----
Sleyp et al. 2022 (PMID: 36214804) reported on 14 patients with de novo missense variants who all presented with mild to severe ID, seizures, ASD, hyperactivity, and dysmorphic facial features. One variant (c.1069G>A, p.Gly357Arg) was recurrent in 11/14 cases but all variants clustered in the Kelch-type β-propeller domain (substrate binding surface) of the KLHL20 protein. No functional studies were performed but given the overlap in clinical presentation observed in patients with the same recurrent variant but also multiple different variants, its worth including as diagnostic-grade.
Intellectual disability v4.18 KLHL20 Arina Puzriakova Gene: klhl20 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.17 KCNK3 Arina Puzriakova Classified gene: KCNK3 as Amber List (moderate evidence)
Intellectual disability v4.17 KCNK3 Arina Puzriakova Added comment: Comment on list classification: Given the number of unrelated cases with a comparable phenotype, all shown to have variants that cluster near the X-gate and cause increased channel activation, this gene should be promoted to Green status at the next GMS panel update.

The overall phenotype is likely most compatible with the Paediatric disorders super panel, and addition to the ID panel will ensure this genes' inclusion.
Intellectual disability v4.17 KCNK3 Arina Puzriakova Gene: kcnk3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.16 KCNK3 Arina Puzriakova gene: KCNK3 was added
gene: KCNK3 was added to Intellectual disability. Sources: Literature
Q4_22_promote_green tags were added to gene: KCNK3.
Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNK3 were set to 36195757
Phenotypes for gene: KCNK3 were set to Developmental disorder with sleep apnea
Mode of pathogenicity for gene: KCNK3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added comment: Heterozygous variant in the KCNK3 gene already have a well-established link with pulmonary arterial hypertension (OMIM:615344).

However, Sormann et al. 2022 (PMID: 36195757) identified nine unrelated individuals harbouring one of six de novo missense variants in KCNK3 who presented with developmental delay and sleep apnea among other variable features (musculoskeletal and limb anomalies, abnormalities of male genitalia/groin and digestive disturbance). The variants were shown to cause defective X-gating leading to overactive channels that no longer respond to inhibition by G-protein-coupled receptor pathways (i.e. GOF), distinct from the PAH mechanism which is caused by LOF variants.
Sources: Literature
Intellectual disability v4.15 RPL10 Dmitrijs Rots reviewed gene: RPL10: 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: 35876338; Phenotypes: ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v4.15 FRMD5 Arina Puzriakova Classified gene: FRMD5 as Amber List (moderate evidence)
Intellectual disability v4.15 FRMD5 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 8 unrelated cases plus supportive fly model.
Intellectual disability v4.15 FRMD5 Arina Puzriakova Gene: frmd5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.14 FRMD5 Arina Puzriakova gene: FRMD5 was added
gene: FRMD5 was added to Intellectual disability. Sources: Literature
Q4_22_promote_green tags were added to gene: FRMD5.
Mode of inheritance for gene: FRMD5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FRMD5 were set to 36206744
Phenotypes for gene: FRMD5 were set to Neurodevelopmental disorder with eye movement abnormalities and ataxia, OMIM:620094
Review for gene: FRMD5 was set to GREEN
Added comment: Lu et al. 2022 (PMID: 36206744) report 8 unrelated individuals with de novo missense FRMD5 variants who presented with developmental delay (8/8), intellectual disability (7/7), ataxia (7/8), seizures (5/8), and abnormalities of eye movement (8/8). LOF mutant flies exhibited motor impairment, defective responses to light and heat-induced seizures. Fly phenotypes were rescued by expression of the wildtype gene but not by two of the patient missense mutants.

FRMD5 is associated with a relevant phenotype in OMIM (MIM# 620094) but is not yet listed in G2P.
Sources: Literature
Intellectual disability v4.13 CAPRIN1 Dmitrijs Rots reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36136249; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.13 BUB1 Sarah Leigh edited their review of gene: BUB1: Added comment: Not associated with a phenotype in OMIM, but has a moderate association with BUB1-related microcephaly and developmental disorder in Gen2Phen. PMID: 35044816 reports three BUB1 variants in two cases of developmental delay, including microcephaly, together with supportive functional studies.; Changed rating: GREEN
Intellectual disability v4.13 SLC35F1 Arina Puzriakova Classified gene: SLC35F1 as Red List (low evidence)
Intellectual disability v4.13 SLC35F1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Rating Red as only a single patient with a heterozygous missense variant has been reported to date (PMID:33821533). Limited information on the SLC35F1 gene is known in general.
Intellectual disability v4.13 SLC35F1 Arina Puzriakova Gene: slc35f1 has been classified as Red List (Low Evidence).
Intellectual disability v4.12 BUB1 Sarah Leigh Tag Q4_22_MOI tag was added to gene: BUB1.
Tag Q4_22_promote_green tag was added to gene: BUB1.
Intellectual disability v4.12 BUB1 Sarah Leigh Classified gene: BUB1 as Amber List (moderate evidence)
Intellectual disability v4.12 BUB1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.12 BUB1 Sarah Leigh Gene: bub1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.11 TPR Achchuthan Shanmugasundram gene: TPR was added
gene: TPR was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPR were set to 34494102
Phenotypes for gene: TPR were set to Intellectual disability, MONDO:0001071
Review for gene: TPR was set to RED
Added comment: Comment on classification of this gene: This gene should be added with a RED rating as the association of TPR to intellectual disability is based on biallelic variants identified from a report of two siblings.

Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability.

Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v4.10 BAP1 Mafalda Gomes edited their review of gene: BAP1: Changed phenotypes to: Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.10 BAP1 Mafalda Gomes reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35051358; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.10 SUFU Arina Puzriakova edited their review of gene: SUFU: Changed publications to: 21289193, 28965847, 33024317, 34675124
Intellectual disability v4.10 SUFU Arina Puzriakova Penetrance for gene SUFU was set from to None
Intellectual disability v4.9 SUFU Arina Puzriakova Classified gene: SUFU as Amber List (moderate evidence)
Intellectual disability v4.9 SUFU Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update under a MONOALLELIC inheritance pattern only, unless the NHS GMS working group disagree and feel the MOI should include both mono- and biallelic variants based on the current evidence.
Intellectual disability v4.9 SUFU Arina Puzriakova Gene: sufu has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.8 SUFU Arina Puzriakova Publications for gene: SUFU were set to 21289193; 28965847; 33024317, 34675124
Intellectual disability v4.7 SUFU Arina Puzriakova Added comment: Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical team) it was decided that based on the current evidence the MOI should be set to 'monoallelic' only for now but with a 'watchlist' tag to monitor for additional biallelic cases relating to a Joubert-like presentation.
Intellectual disability v4.7 SUFU Arina Puzriakova Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.6 SUFU Arina Puzriakova Publications for gene: SUFU were set to 28965847; 30914295
Intellectual disability v4.5 SUFU Arina Puzriakova Phenotypes for gene: SUFU were changed from Joubert syndrome 32, 617757 to Joubert syndrome 32, OMIM:617757
Intellectual disability v4.4 SUFU Arina Puzriakova Tag Q4_22_MOI tag was added to gene: SUFU.
Intellectual disability v4.4 SUFU Arina Puzriakova Tag watchlist was removed from gene: SUFU.
Tag watchlist_moi tag was added to gene: SUFU.
Tag Q4_22_promote_green tag was added to gene: SUFU.
Intellectual disability v4.4 SUFU Arina Puzriakova edited their review of gene: SUFU: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.4 SUFU Arina Puzriakova reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: 21289193, 28965847, 33024317, 34675124; Phenotypes: Joubert syndrome 32, OMIM:617757; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.4 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from SHOX deficiency (with Intellectual disability) to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582
Intellectual disability v4.3 SHOX Arina Puzriakova Mode of inheritance for gene: SHOX was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability v4.2 KLHL20 Dmitrijs Rots gene: KLHL20 was added
gene: KLHL20 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KLHL20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLHL20 were set to 36214804
Phenotypes for gene: KLHL20 were set to developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder
Penetrance for gene: KLHL20 were set to unknown
Mode of pathogenicity for gene: KLHL20 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: KLHL20 was set to GREEN
Added comment: More 14 individuals with mostly recurrent missense variant reported in KLHL20
Sources: Literature
Intellectual disability v4.2 PAX6 Tracy Lester reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.2 RARB Zornitza Stark reviewed gene: RARB: Rating: GREEN; Mode of pathogenicity: None; Publications: 30880327, 30281527, 24075189, 27120018, 25457163, 17506106; Phenotypes: Microphthalmia, syndromic 12, MIM# 615524, Neurodevelopmental disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.2 BLM Zornitza Stark reviewed gene: BLM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bloom syndrome, MIM# 210900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.2 PRSS12 Sarah Leigh Publications for gene: PRSS12 were set to
Intellectual disability v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2022-11-30
Intellectual disability v4.0 Eleanor Williams promoted panel to version 4.0
Intellectual disability v3.1771 RARB Dmitrijs Rots reviewed gene: RARB: Rating: ; 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: 27120018; Phenotypes: Intellectual Disability with Progressive Motor Impairment; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.1771 FBXW7 Arina Puzriakova Phenotypes for gene: FBXW7 were changed from Neurodevelopmental abnormality; Global developmental delay; Intellectual disability; Macrocephaly; Microcephaly; Abnormality of brain morphology; Abnormality of the corpus callosum; Abnormality of the cerebellum; Abnormality of the cardiovascular system; Seizures; Strabismus; Abnormality of the palate to Developmental delay, hypotonia, and impaired language, OMIM:620012
Intellectual disability v3.1770 TAB2 Arina Puzriakova Phenotypes for gene: TAB2 were changed from Congenital heart defects, nonsyndromic, 2, 614980 to Congenital heart defects, nonsyndromic, 2, OMIM:614980
Intellectual disability v3.1769 JARID2 Eleanor Williams commented on gene: JARID2
Intellectual disability v3.1769 JARID2 Eleanor Williams Phenotypes for gene: JARID2 were changed from Intellectual disability; Neurodevelopmental syndrome to Intellectual disability; Neurodevelopmental syndrome; Developmental delay with variable intellectual disability and dysmorphic facies, OMIM:620098
Intellectual disability v3.1768 JARID2 Eleanor Williams Tag gene-checked was removed from gene: JARID2.
Intellectual disability v3.1768 HNRNPR Eleanor Williams commented on gene: HNRNPR
Intellectual disability v3.1768 HNRNPR Eleanor Williams Phenotypes for gene: HNRNPR were changed from Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly; Short digit to Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly; Short digit; Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, OMIM:620073
Intellectual disability v3.1767 HNRNPR Eleanor Williams Tag gene-checked was removed from gene: HNRNPR.
Intellectual disability v3.1767 HNRNPH1 Eleanor Williams commented on gene: HNRNPH1
Intellectual disability v3.1767 HNRNPH1 Eleanor Williams Phenotypes for gene: HNRNPH1 were changed from HNRNPH1‐related syndromic intellectual disability to HNRNPH1‐related syndromic intellectual disability; Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, OMIM:620083
Intellectual disability v3.1766 HNRNPH1 Eleanor Williams Tag gene-checked was removed from gene: HNRNPH1.
Intellectual disability v3.1766 HID1 Eleanor Williams commented on gene: HID1
Intellectual disability v3.1766 HID1 Eleanor Williams Phenotypes for gene: HID1 were changed from Syndromic infantile encephalopathy; Hypopituitarism to Syndromic infantile encephalopathy; Hypopituitarism; Developmental and epileptic encephalopathy 105 with hypopituitarism, OMIM:619983
Intellectual disability v3.1765 HID1 Eleanor Williams Tag gene-checked was removed from gene: HID1.
Intellectual disability v3.1765 CACNA1I Eleanor Williams commented on gene: CACNA1I
Intellectual disability v3.1765 CACNA1I Eleanor Williams Phenotypes for gene: CACNA1I were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with speech impairment and with or without seizures, OMIM:620114
Intellectual disability v3.1764 CACNA1I Eleanor Williams Tag gene-checked was removed from gene: CACNA1I.
Intellectual disability v3.1764 ARFGEF1 Eleanor Williams commented on gene: ARFGEF1
Intellectual disability v3.1764 ARFGEF1 Eleanor Williams Tag gene-checked was removed from gene: ARFGEF1.
Intellectual disability v3.1764 ARFGEF1 Eleanor Williams Phenotypes for gene: ARFGEF1 were changed from Intellectual disability, MONDO:0001071; Epilepsy, MONDO:0005027 to Intellectual disability, MONDO:0001071; Epilepsy, MONDO:0005027; Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures, OMIM:619964
Intellectual disability v3.1763 DDX58 Eleanor Williams commented on gene: DDX58
Intellectual disability v3.1763 DDX58 Eleanor Williams Tag new-gene-name tag was added to gene: DDX58.
Intellectual disability v3.1763 FAM126A Eleanor Williams commented on gene: FAM126A
Intellectual disability v3.1763 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
Intellectual disability v3.1763 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal recessive 4 to Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Intellectual disability v3.1762 RAD21 Arina Puzriakova Publications for gene: RAD21 were set to
Intellectual disability v3.1761 RAD21 Arina Puzriakova Phenotypes for gene: RAD21 were changed from Cornelia de Lange syndrome 4, 614701; COHESINOPATHY to Cornelia de Lange syndrome 4, OMIM:614701
Intellectual disability v3.1760 FMR1 Arina Puzriakova Publications for gene: FMR1 were set to
Intellectual disability v3.1759 FMR1 Arina Puzriakova reviewed gene: FMR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21267007, 25171808, 28176767, 29178241; Phenotypes: ; 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 v3.1759 FOXP4 Ian Berry reviewed gene: FOXP4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33110267; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.1759 AGO1 Arina Puzriakova Publications for gene: AGO1 were set to 26350204; 30213762; 22495306; 23020937; 25363768; 25356899; 27620904; 29346770; 28135719
Intellectual disability v3.1758 CTNNB1 Arina Puzriakova Publications for gene: CTNNB1 were set to
Intellectual disability v3.1757 CTNNB1 Arina Puzriakova Phenotypes for gene: CTNNB1 were changed from Mental retardation, autosomal dominant 19, 615075Colorectal cancer, somatic, 114500Pilomatricoma, somatic, 132600Ovarian cancer, somatic, 167000Hepatocellular carcinoma, somatic, 114550; MENTAL RETARDATION, AUTOSOMAL DOMINANT 19 to Neurodevelopmental disorder with spastic diplegia and visual defects, OMIM:615075
Intellectual disability v3.1756 HK1 Arina Puzriakova Phenotypes for gene: HK1 were changed from Neurodevelopmental disorder with visual defects and brain anomalies, OMIM:618547; neurodevelopmental disorder with visual defects and brain anomalies, MONDO:0032807 to Neurodevelopmental disorder with visual defects and brain anomalies, OMIM:618547
Intellectual disability v3.1755 GRM1 Arina Puzriakova Phenotypes for gene: GRM1 were changed from Spinocerebellar ataxia, autosomal recessive 13, 614831; CONGENITAL CEREBELLAR ATAXIA to Spinocerebellar ataxia, autosomal recessive 13, OMIM:614831
Intellectual disability v3.1754 GRM1 Arina Puzriakova Publications for gene: GRM1 were set to
Intellectual disability v3.1753 GPHN Arina Puzriakova Publications for gene: GPHN were set to
Intellectual disability v3.1752 GPHN Arina Puzriakova Phenotypes for gene: GPHN were changed from Molybdenum cofactor deficiency C to Molybdenum cofactor deficiency C, OMIM:615501
Intellectual disability v3.1751 GPHN Arina Puzriakova Mode of inheritance for gene: GPHN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.1750 GATM Arina Puzriakova Phenotypes for gene: GATM were changed from Cerebral creatine deficiency syndrome 3, 612718; ARGININE:GLYCINE AMIDINOTRANSFERASE DEFICIENCY (AGAT DEFICIENCY) to Cerebral creatine deficiency syndrome 3, OMIM:612718
Intellectual disability v3.1749 ADAR Arina Puzriakova Phenotypes for gene: ADAR were changed from Dyschromatosis symmetrica hereditaria, 127400Aicardi-Goutieres syndrome 6, 615010; DYSCHROMATOSIS SYMMETRICA HEREDITARIA 1 to Aicardi-Goutieres syndrome 6, OMIM:615010; Dyschromatosis symmetrica hereditaria, OMIM:127400
Intellectual disability v3.1748 ADAR Arina Puzriakova reviewed gene: ADAR: Rating: ; Mode of pathogenicity: None; Publications: 16225627, 16817193, 19017046; Phenotypes: Aicardi-Goutieres syndrome 6, OMIM:615010, Dyschromatosis symmetrica hereditaria, OMIM:127400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.1748 FBXW7 Julia Baptista reviewed gene: FBXW7: Rating: GREEN; Mode of pathogenicity: None; Publications: 35395208; Phenotypes: developmental delay, ID, language disorder, hypotonia, brain anomalies, gastrointestinal issues; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.1748 ACOX1 Arina Puzriakova Added comment: Comment on mode of inheritance: Adding 'watchlist_moi' tag to monitor for evidence supporting association of monoallelic variants in this gene with ID. To date, three unrelated cases have been reported (PMID: 32169171) with dominant variants. Two patients had impaired cognition while one remained cognitively intact. These cases should be picked up via other routes (neuropathy, hearing loss) but monitoring evidence pertaining to monoallelic variants may be of value.
Intellectual disability v3.1748 ACOX1 Arina Puzriakova Mode of inheritance for gene: ACOX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1747 ACOX1 Arina Puzriakova Tag watchlist_moi tag was added to gene: ACOX1.
Intellectual disability v3.1747 ACOX1 Arina Puzriakova Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, 264470; ADRENOLEUKODYSTROPHY PSEUDONEONATAL (PSEUDO-NALD) to Peroxisomal acyl-CoA oxidase deficiency, OMIM:264470; Mitchell syndrome, OMIM:618960
Intellectual disability v3.1746 ADAR Tracy Lester reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, developmental delay, delayed speech and language, learning disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1746 BAP1 Rachel Challis gene: BAP1 was added
gene: BAP1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAP1 were set to 35051358
Phenotypes for gene: BAP1 were set to Intellectual disability; short stature; autism spectrum disorder
Review for gene: BAP1 was set to GREEN
gene: BAP1 was marked as current diagnostic
Added comment: 11 de novo BAP1 missense variants identified predominantly in UCH domain. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. Analysis of blood from affected patients demonstrated impaired H2A deubiquitination compared to controls.
Sources: Literature
Intellectual disability v3.1746 YARS Dmitrijs Rots changed review comment from: 12 patients with homozygous p.(Arg367Trp) have distinct NDD reported in PMID: 34536092.; to: 12 patients with homozygous p.(Arg367Trp) have distinct NDD reported in PMID: 34536092.
Intellectual disability v3.1746 YARS Dmitrijs Rots reviewed gene: YARS: Rating: ; Mode of pathogenicity: None; Publications: PMID: 34536092; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.1746 GNAS Sarah Leigh Phenotypes for gene: GNAS were changed from Pseudohypoparathyroidism Ia, 103580McCune-Albright syndrome, 174800Pseudohypoparathyroidism Ic, 612462Osseous heteroplasia, progressive, 166350Pseudohypoparathyroidism Ib, 603233Prolonged bleeding time, brachydactyly and mental retardationAcromegaly, 102200Pseudopseudohypoparathyroidism, 612463Prolonged bleeding time, brachydactyly, and mental retardationACTH-independent macronodular adrenal hyperplasia, 219080; ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA (AIMAH) to Pseudohypoparathyroidism Ia, OMIM:103580; pseudohypoparathyroidism type 1A, MONDO:0007078; Pseudohypoparathyroidism Ic, OMIM:612462; pseudohypoparathyroidism type 1C, MONDO:0012911; Pseudopseudohypoparathyroidism, OMIM:612463; pseudopseudohypoparathyroidism, MONDO:0012912
Intellectual disability v3.1745 GNAS Sarah Leigh Added comment: Comment on mode of inheritance: Disease causing variants in the GNAS locus have differing expression panels. Pseudohypothyroidism Ia & Ic are all caused by GNAS variants arising in the maternal alleles, therefore, the mode of inheritance (MOI) for GNAS in these conditions should be monoallelic maternally imprinted. Pseudopseudohypoparathyroidism, OMIM:612463 is associated with variants in the paternal alleles therefore, the mode of inheritance for GNAS in this condition should be monoallelic paternally imprinted. Because intellectual disability is seen in these phenotypes, the MOI has been set to monoallelic, imprinted status unknown.
Intellectual disability v3.1745 GNAS Sarah Leigh Mode of inheritance for gene: GNAS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v3.1744 AP1S2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles.

As no confirmed female cases have been reported and the allelic requirement remains elusive, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease) as this will ensure that both mono and biallelic variants are picked up in females by the pipeline.; to: Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles.

As it is not known definitively whether females require a variant on each allele of this gene in order to be affected, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease).
Intellectual disability v3.1744 ROR2 Arina Puzriakova Classified gene: ROR2 as Green List (high evidence)
Intellectual disability v3.1744 ROR2 Arina Puzriakova Added comment: Comment on list classification: Following a Red review by Tracy Lester (Genetics laboratory, Oxford UK) this gene was re-curated showing the neurocognitive function in patients with monoallelic and biallelic variants is typically normal. Cases are more likely to be picked up via skeletal abnormalities route. Therefore, ROR2 should be downgraded to Red on this panel at the next GMS panel update.
Intellectual disability v3.1744 ROR2 Arina Puzriakova Gene: ror2 has been classified as Green List (High Evidence).
Intellectual disability v3.1743 ROR2 Arina Puzriakova Tag Q4_22_demote_red tag was added to gene: ROR2.
Tag Q4_22_NHS_review tag was added to gene: ROR2.
Intellectual disability v3.1743 ROR2 Arina Puzriakova Phenotypes for gene: ROR2 were changed from BRACHYDACTYLY, TYPE B1 to Brachydactyly, type B1, OMIM:113000 (AD); Robinow syndrome, autosomal recessive, OMIM:268310 (AR)
Intellectual disability v3.1742 PDZD8 Eleanor Williams commented on gene: PDZD8
Intellectual disability v3.1742 PDZD8 Eleanor Williams Tag Q3_22_MOI was removed from gene: PDZD8.