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Intellectual disability syndromic and non-syndromic v0.6377 MTFMT Zornitza Stark Publications for gene: MTFMT were set to 21907147; 23499752; 24461907; 22499348
Intellectual disability syndromic and non-syndromic v0.6376 MTFMT Zornitza Stark Publications for gene: MTFMT were set to
Intellectual disability syndromic and non-syndromic v0.6375 MTFMT Zornitza Stark Mode of inheritance for gene: MTFMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6374 MVK Zornitza Stark Marked gene: MVK as ready
Intellectual disability syndromic and non-syndromic v0.6374 MVK Zornitza Stark Gene: mvk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6374 MVK Zornitza Stark Phenotypes for gene: MVK were changed from to Hyper-IgD syndrome (MIM#260920); Mevalonic aciduria (MIM#610377)
Intellectual disability syndromic and non-syndromic v0.6374 MVK Zornitza Stark Publications for gene: MVK were set to 29047407; 26409462
Intellectual disability syndromic and non-syndromic v0.6373 MVK Zornitza Stark Publications for gene: MVK were set to 29047407; 26409462
Intellectual disability syndromic and non-syndromic v0.6373 MVK Zornitza Stark Publications for gene: MVK were set to
Intellectual disability syndromic and non-syndromic v0.6373 MVK Zornitza Stark Mode of inheritance for gene: MVK was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6372 MVK Zornitza Stark Mode of inheritance for gene: MVK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6371 MYO5A Zornitza Stark Marked gene: MYO5A as ready
Intellectual disability syndromic and non-syndromic v0.6371 MYO5A Zornitza Stark Gene: myo5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6371 MYO5A Zornitza Stark Phenotypes for gene: MYO5A were changed from to Griscelli syndrome, type 1 MIM#214450
Intellectual disability syndromic and non-syndromic v0.6370 MYO5A Zornitza Stark Publications for gene: MYO5A were set to
Intellectual disability syndromic and non-syndromic v0.6369 MYO5A Zornitza Stark Mode of inheritance for gene: MYO5A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6368 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Intellectual disability syndromic and non-syndromic v0.6368 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6368 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from to Homocystinuria due to MTHFR deficiency MIM#236250; Disorders of folate metabolism and transport
Intellectual disability syndromic and non-syndromic v0.6367 MTHFR Zornitza Stark Publications for gene: MTHFR were set to
Intellectual disability syndromic and non-syndromic v0.6366 MTHFR Zornitza Stark Mode of inheritance for gene: MTHFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6365 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Intellectual disability syndromic and non-syndromic v0.6365 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6365 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from to Niemann-pick disease, type C2, MIM# 607625; MONDO:0011873
Intellectual disability syndromic and non-syndromic v0.6364 NPC2 Zornitza Stark Publications for gene: NPC2 were set to 11125141; 17470133
Intellectual disability syndromic and non-syndromic v0.6363 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Intellectual disability syndromic and non-syndromic v0.6362 NPC2 Zornitza Stark Mode of inheritance for gene: NPC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6361 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Intellectual disability syndromic and non-syndromic v0.6361 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6361 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from to Niemann-Pick disease, type C1 and type D, MIM# 257220; MONDO:0009757
Intellectual disability syndromic and non-syndromic v0.6360 NPC1 Zornitza Stark Publications for gene: NPC1 were set to
Intellectual disability syndromic and non-syndromic v0.6359 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6358 NKX2-1 Zornitza Stark Marked gene: NKX2-1 as ready
Intellectual disability syndromic and non-syndromic v0.6358 NKX2-1 Zornitza Stark Gene: nkx2-1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6358 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978 to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978
Intellectual disability syndromic and non-syndromic v0.6357 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978
Intellectual disability syndromic and non-syndromic v0.6356 NKX2-1 Zornitza Stark Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969; 23911641; 11854319; 24714694
Intellectual disability syndromic and non-syndromic v0.6355 NKX2-1 Zornitza Stark Publications for gene: NKX2-1 were set to
Intellectual disability syndromic and non-syndromic v0.6354 NKX2-1 Zornitza Stark Mode of inheritance for gene: NKX2-1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6353 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
Intellectual disability syndromic and non-syndromic v0.6353 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6353 NGLY1 Zornitza Stark Phenotypes for gene: NGLY1 were changed from to Congenital disorder of deglycosylation (OMIM 615273)
Intellectual disability syndromic and non-syndromic v0.6352 NGLY1 Zornitza Stark reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24651605, 27388694, 32259258; Phenotypes: Congenital disorder of deglycosylation (OMIM 615273); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6352 NGLY1 Zornitza Stark Publications for gene: NGLY1 were set to
Intellectual disability syndromic and non-syndromic v0.6351 NGLY1 Zornitza Stark Mode of inheritance for gene: NGLY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6350 NFIX Zornitza Stark Marked gene: NFIX as ready
Intellectual disability syndromic and non-syndromic v0.6350 NFIX Zornitza Stark Gene: nfix has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6350 NFIX Zornitza Stark Phenotypes for gene: NFIX were changed from to Sotos syndrome 2 (MIM#614753); Marshall-Smith syndrome, MIM# 602535
Intellectual disability syndromic and non-syndromic v0.6349 NFIX Zornitza Stark Publications for gene: NFIX were set to 33034087; 29897170; 30548146; 25118028
Intellectual disability syndromic and non-syndromic v0.6348 NFIX Zornitza Stark Publications for gene: NFIX were set to
Intellectual disability syndromic and non-syndromic v0.6347 NFIX Zornitza Stark Mode of inheritance for gene: NFIX was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6346 NEU1 Zornitza Stark Marked gene: NEU1 as ready
Intellectual disability syndromic and non-syndromic v0.6346 NEU1 Zornitza Stark Gene: neu1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6346 NEU1 Zornitza Stark Phenotypes for gene: NEU1 were changed from to Sialidosis, type I and type II, MIM# 256550; MONDO:0009738
Intellectual disability syndromic and non-syndromic v0.6345 NEU1 Zornitza Stark Publications for gene: NEU1 were set to
Intellectual disability syndromic and non-syndromic v0.6344 NEU1 Zornitza Stark Mode of inheritance for gene: NEU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6343 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Intellectual disability syndromic and non-syndromic v0.6343 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6343 NDUFV1 Zornitza Stark Phenotypes for gene: NDUFV1 were changed from to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225
Intellectual disability syndromic and non-syndromic v0.6342 NDUFV1 Zornitza Stark Publications for gene: NDUFV1 were set to
Intellectual disability syndromic and non-syndromic v0.6341 NDUFV1 Zornitza Stark Mode of inheritance for gene: NDUFV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6340 NDUFS7 Zornitza Stark Marked gene: NDUFS7 as ready
Intellectual disability syndromic and non-syndromic v0.6340 NDUFS7 Zornitza Stark Gene: ndufs7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6340 NDUFS7 Zornitza Stark Phenotypes for gene: NDUFS7 were changed from to Mitochondrial complex I deficiency, nuclear type 3 (MIM# 618224)
Intellectual disability syndromic and non-syndromic v0.6339 NDUFS7 Zornitza Stark Publications for gene: NDUFS7 were set to
Intellectual disability syndromic and non-syndromic v0.6338 NDUFS7 Zornitza Stark Mode of inheritance for gene: NDUFS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6337 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Intellectual disability syndromic and non-syndromic v0.6337 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6337 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from Mitochondrial complex I deficiency, nuclear type 12 MIM#301020 to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Intellectual disability syndromic and non-syndromic v0.6336 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Intellectual disability syndromic and non-syndromic v0.6335 NDUFA1 Zornitza Stark Publications for gene: NDUFA1 were set to
Intellectual disability syndromic and non-syndromic v0.6334 NDUFA1 Zornitza Stark Mode of inheritance for gene: NDUFA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6333 NALCN Zornitza Stark Marked gene: NALCN as ready
Intellectual disability syndromic and non-syndromic v0.6333 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6333 NALCN Zornitza Stark Phenotypes for gene: NALCN were changed from to Congenital contractures of the limbs and face, hypotonia, and developmental delay, MIM# 616266; Hypotonia, infantile, with psychomotor retardation and characteristic facies 1, MIM # 615419
Intellectual disability syndromic and non-syndromic v0.6332 NALCN Zornitza Stark Publications for gene: NALCN were set to
Intellectual disability syndromic and non-syndromic v0.6331 NALCN Zornitza Stark Mode of inheritance for gene: NALCN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6330 NAGLU Zornitza Stark Marked gene: NAGLU as ready
Intellectual disability syndromic and non-syndromic v0.6330 NAGLU Zornitza Stark Gene: naglu has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6330 NAGLU Zornitza Stark Phenotypes for gene: NAGLU were changed from to Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920
Intellectual disability syndromic and non-syndromic v0.6329 NAGLU Zornitza Stark Publications for gene: NAGLU were set to
Intellectual disability syndromic and non-syndromic v0.6328 NAGLU Zornitza Stark Mode of inheritance for gene: NAGLU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6327 NAGA Zornitza Stark Marked gene: NAGA as ready
Intellectual disability syndromic and non-syndromic v0.6327 NAGA Zornitza Stark Gene: naga has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6327 NAGA Zornitza Stark Phenotypes for gene: NAGA were changed from Kanzaki disease, MIM# 609242; Schindler disease, type I and type II 609241; alpha-N-acetylgalactosaminidase deficiency MONDO:0017779 to Kanzaki disease, MIM# 609242; Schindler disease, type I and type II 609241; alpha-N-acetylgalactosaminidase deficiency MONDO:0017779
Intellectual disability syndromic and non-syndromic v0.6327 NAGA Zornitza Stark Phenotypes for gene: NAGA were changed from to Kanzaki disease, MIM# 609242; Schindler disease, type I and type II 609241; alpha-N-acetylgalactosaminidase deficiency MONDO:0017779
Intellectual disability syndromic and non-syndromic v0.6326 NAGA Zornitza Stark Publications for gene: NAGA were set to
Intellectual disability syndromic and non-syndromic v0.6325 NAGA Zornitza Stark Mode of inheritance for gene: NAGA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6324 SCO2 Zornitza Stark Marked gene: SCO2 as ready
Intellectual disability syndromic and non-syndromic v0.6324 SCO2 Zornitza Stark Gene: sco2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6324 SCO2 Zornitza Stark Phenotypes for gene: SCO2 were changed from to Mitochondrial complex IV deficiency, nuclear type 2, MIM# 604377
Intellectual disability syndromic and non-syndromic v0.6323 SCO2 Zornitza Stark Publications for gene: SCO2 were set to
Intellectual disability syndromic and non-syndromic v0.6322 SCO2 Zornitza Stark Mode of inheritance for gene: SCO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6321 SKI Zornitza Stark Marked gene: SKI as ready
Intellectual disability syndromic and non-syndromic v0.6321 SKI Zornitza Stark Gene: ski has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6321 SKI Zornitza Stark Phenotypes for gene: SKI were changed from to Shprintzen-Goldberg syndrome, MIM# 182212; Neurodevelopmental disorder, MONDO:0700092, SKI-related
Intellectual disability syndromic and non-syndromic v0.6320 SKI Zornitza Stark Publications for gene: SKI were set to
Intellectual disability syndromic and non-syndromic v0.6319 SKI Zornitza Stark Mode of inheritance for gene: SKI was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6318 SKI Zornitza Stark reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, SKI-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6318 SHH Zornitza Stark Marked gene: SHH as ready
Intellectual disability syndromic and non-syndromic v0.6318 SHH Zornitza Stark Gene: shh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6318 SHH Zornitza Stark Phenotypes for gene: SHH were changed from to Holoprosencephaly 3 (MIM#142945)
Intellectual disability syndromic and non-syndromic v0.6317 SHH Zornitza Stark Publications for gene: SHH were set to
Intellectual disability syndromic and non-syndromic v0.6316 SHH Zornitza Stark Mode of inheritance for gene: SHH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6315 LRRC7 Zornitza Stark Marked gene: LRRC7 as ready
Intellectual disability syndromic and non-syndromic v0.6315 LRRC7 Zornitza Stark Gene: lrrc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6315 LRRC7 Zornitza Stark Phenotypes for gene: LRRC7 were changed from neurodevelopmental disorder (MONDO:0700092) to neurodevelopmental disorder (MONDO:0700092), LRRC7-related
Intellectual disability syndromic and non-syndromic v0.6314 LRRC7 Zornitza Stark reviewed gene: LRRC7: Rating: GREEN; Mode of pathogenicity: None; Publications: 39256359; Phenotypes: neurodevelopmental disorder (MONDO:0700092), LRRC7-related; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.6314 LRRC7 Zornitza Stark Classified gene: LRRC7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6314 LRRC7 Zornitza Stark Gene: lrrc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6313 SECISBP2 Zornitza Stark Phenotypes for gene: SECISBP2 were changed from #609698 THYROID HORMONE METABOLISM, ABNORMAL to Thyroid hormone metabolism, abnormal, 1, MIM# 609698
Intellectual disability syndromic and non-syndromic v0.6312 SECISBP2 Zornitza Stark Publications for gene: SECISBP2 were set to 16228000; 19602558; 21084748; 22247018
Intellectual disability syndromic and non-syndromic v0.6311 SECISBP2 Zornitza Stark Classified gene: SECISBP2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6311 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6310 SECISBP2 Zornitza Stark reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39315526; Phenotypes: Thyroid hormone metabolism, abnormal, 1, MIM# 609698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6310 FLVCR1 Bryony Thompson Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, MIM#609033 to neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Intellectual disability syndromic and non-syndromic v0.6309 FLVCR1 Bryony Thompson Publications for gene: FLVCR1 were set to
Intellectual disability syndromic and non-syndromic v0.6308 FLVCR1 Bryony Thompson Classified gene: FLVCR1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6308 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6307 FLVCR1 Bryony Thompson reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39306721; Phenotypes: neurodevelopmental disorder MONDO:0700092, FLVCR1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6307 LRRC7 Sangavi Sivagnanasundram gene: LRRC7 was added
gene: LRRC7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LRRC7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC7 were set to 39256359
Phenotypes for gene: LRRC7 were set to neurodevelopmental disorder (MONDO:0700092)
Review for gene: LRRC7 was set to GREEN
Added comment: Well established gene-disease association.
Neurodevelopmental disorder with a clinical spectrum - symptoms include ID, ADHD, aggression and in many cases, hyperphagia associate obesity.
Heterozygous missense and LoF variants have been reported and functional assays were conducted on missense and truncating variants that support LoF mechanism of disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6307 SHH Chirag Patel reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22791840, 19057928; Phenotypes: Holoprosencephaly 3 (MIM#142945); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6307 SKI Chirag Patel reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23023332, 23103230, 24736733, 30071989; Phenotypes: Shprintzen-Goldberg syndrome, MIM# 182212; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6307 SCO2 Chirag Patel reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10545952, 10749987, 18924171; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 2, MIM# 604377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6307 NAGA Chirag Patel reviewed gene: NAGA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11313741, 31468281, 15619430, 8782044; Phenotypes: Kanzaki disease, MIM# 609242, Schindler disease, type I and type II 609241, alpha-N-acetylgalactosaminidase deficiency MONDO:0017779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6307 NAGLU Chirag Patel reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8650226; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6307 NALCN Chirag Patel reviewed gene: NALCN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25683120, 30167850, 23749988, 24075186; Phenotypes: Congenital contractures of the limbs and face, hypotonia, and developmental delay, MIM# 616266, Hypotonia, infantile, with psychomotor retardation and characteristic facies 1, MIM # 615419; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6307 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968) to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Intellectual disability syndromic and non-syndromic v0.6306 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575) to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Intellectual disability syndromic and non-syndromic v0.6305 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; Nephrotic syndrome, type 14, MIM#617575 to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Intellectual disability syndromic and non-syndromic v0.6304 NDUFA1 Chirag Patel reviewed gene: NDUFA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29506883, 19185523, 17262856, 21596602; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6304 NDUFS7 Chirag Patel reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22644603; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 (MIM# 618224); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NDUFS8 Chirag Patel reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23430795, 9837812, 15159508, 22499348, 20818383, 20819849; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 MIM#618222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NDUFV1 Chirag Patel reviewed gene: NDUFV1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34807224; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NEU1 Chirag Patel reviewed gene: NEU1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8985184, 9054950, 11063730; Phenotypes: Sialidosis, type I and type II, MIM# 256550, MONDO:0009738; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NFIX Chirag Patel reviewed gene: NFIX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33034087, 29897170, 30548146, 25118028; Phenotypes: Sotos syndrome 2 (MIM#614753), Marshall-Smith syndrome, MIM# 602535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6304 NGLY1 Chirag Patel reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: Congenital disorder of deglycosylation (OMIM 615273); Phenotypes: PMID: 24651605, 27388694, 32259258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NKX2-1 Chirag Patel reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10931427, 27066577, 26839702, 26103969, 23911641, 11854319, 24714694; Phenotypes: Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978, Chorea, hereditary benign MIM#118700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6304 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35, MIM#616355 to Houge-Janssens syndrome 1, MIM#616355
Intellectual disability syndromic and non-syndromic v0.6303 NPC1 Chirag Patel reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9211849, 11333381; Phenotypes: Niemann-Pick disease, type C1 and type D, MIM# 257220, MONDO:0009757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 NPC2 Chirag Patel reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11125141, 17470133; Phenotypes: Niemann-pick disease, type C2, MIM# 607625, MONDO:0011873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MTHFR Chirag Patel commented on gene: MTHFR: Well-established gene-disease association (see OMIM entry). Homocystinuria due to MTHFR deficiency is classified as a metabolic disorder by NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders) and is an inborn error of folate metabolism. DD/ID can be seen in condition.
Intellectual disability syndromic and non-syndromic v0.6303 MTHFR Chirag Patel reviewed gene: MTHFR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27604308, 7920641; Phenotypes: Homocystinuria due to MTHFR deficiency MIM#236250, Disorders of folate metabolism and transport; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MYO5A Chirag Patel reviewed gene: MYO5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32275080, 22711375, 25283056; Phenotypes: Griscelli syndrome, type 1 MIM#214450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 RAB27A Chirag Patel reviewed gene: RAB27A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.6303 MVK Chirag Patel reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29047407, 26409462; Phenotypes: Hyper-IgD syndrome (MIM#260920), Mevalonic aciduria (MIM#610377); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MTFMT Chirag Patel reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21907147, 23499752, 24461907, 22499348; Phenotypes: Combined oxidative phosphorylation deficiency 15, MIM# 614947, Mitochondrial complex I deficiency, nuclear type 27, MIM# 618248; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MRPS22 Chirag Patel reviewed gene: MRPS22: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29566152,17873122, 25663021, 28752220; Phenotypes: Combined oxidative phosphorylation deficiency 5 MIM#611719, Ovarian dysgenesis 7 MIM#618117; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MOCS2 Chirag Patel reviewed gene: MOCS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27604308, 10053004; Phenotypes: Molybdenum cofactor deficiency B MIM#252160, Disorders of molybdenum cofactor metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MUT Chirag Patel reviewed gene: MUT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301409, 37420116, 1977311, 11528502, 12948746; Phenotypes: Methylmalonic aciduria, mut(0) type, MIM# 251000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MMADHC Chirag Patel reviewed gene: MMADHC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301409, 37420116,27604308, 18385497; Phenotypes: Homocystinuria, cblD type, variant 1 MIM#277410, Methylmalonic aciduria and homocystinuria, cblD type MIM#277410, Methylmalonic aciduria, cblD type, variant 2 MIM#277410, Disorders of cobalamin absorption, transport and metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MMAB Chirag Patel reviewed gene: MMAB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301409, 37420116; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblB type, MIM# 251110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MMAA Chirag Patel reviewed gene: MMAA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301409, 37420116; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblA type, MIM# 251100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MLC1 Chirag Patel reviewed gene: MLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11254442, 18757878, 16652334; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MKS1 Chirag Patel reviewed gene: MKS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17377820, 24886560, 19776033, 33193692, 27570071, 27377014, 18327255, 24608809; Phenotypes: Joubert syndrome 28, MIM# 617121, MONDO:0014928, Meckel syndrome 1, MIM# 249000, MONDO:0009571, Bardet-Biedl syndrome 13, MIM# 615990, MONDO:0014441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MKKS Chirag Patel reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10973251, 10802661, 26900326; Phenotypes: McKusick-Kaufman syndrome, MIM# 236700, Bardet-Biedl syndrome 6, MIM# 605231, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MBOAT7 Chirag Patel reviewed gene: MBOAT7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33335874, 32645526, 32744787, 31852446, 31282596, 30701556; Phenotypes: Intellectual disability MIM#617188; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MAT1A Chirag Patel reviewed gene: MAT1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27604308, 7560086; Phenotypes: Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency MIM#250850, Methionine adenosyltransferase deficiency, autosomal recessive MIM#250850, Disorders of the metabolism of sulphur amino acids; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MAP2K2 Chirag Patel reviewed gene: MAP2K2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20358587, 16439621, 18042262; Phenotypes: Cardiofaciocutaneous syndrome 3, MIM# 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6303 MAP2K1 Chirag Patel reviewed gene: MAP2K1: 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: 16439621, 17551924, 18042262, 20301365; Phenotypes: Cardiofaciocutaneous syndrome 3, MIM# 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Classified gene: ZDHHC16 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Marked gene: ZDHHC16 as ready
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Classified gene: ZDHHC16 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6302 ZDHHC16 Ain Roesley gene: ZDHHC16 was added
gene: ZDHHC16 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZDHHC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZDHHC16 were set to 39313616
Phenotypes for gene: ZDHHC16 were set to neurodevelopmental disorder MONDO:0700092, ZDHHC16-related
Review for gene: ZDHHC16 was set to AMBER
gene: ZDHHC16 was marked as current diagnostic
Added comment: 6 families including a pair of siblings

Amber because 5 of the families had non specific phenotypes listed
Abnormality of:
the nervous system, metabolism/homeostasis, head/neck, immune system, the integument, the digestive system, the respiratory system, the endocrine system, Growth abnormality the skeletal system, the musculature, the eye

Specific HPOs were provided for one individual (homoyzygous for a canonical splice)

Abnormality of the face; Cerebellar hypoplasia; Developmental regression; Encephalopathy; Hyperreflexia; Hypertonia; Hypotonia; Inguinal hernia; Laryngomalacia; Microcephaly; Motor delay; Optic atrophy; Seizure; Spastic paraparesis; Spasticity; Talipes equinovarus; Umbilical hernia
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6301 EPB41L3 Bryony Thompson Marked gene: EPB41L3 as ready
Intellectual disability syndromic and non-syndromic v0.6301 EPB41L3 Bryony Thompson Gene: epb41l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6301 EPB41L3 Bryony Thompson Classified gene: EPB41L3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6301 EPB41L3 Bryony Thompson Gene: epb41l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6300 EPB41L3 Bryony Thompson gene: EPB41L3 was added
gene: EPB41L3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EPB41L3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPB41L3 were set to 39292993
Phenotypes for gene: EPB41L3 were set to neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities MONDO:0030063
Review for gene: EPB41L3 was set to GREEN
Added comment: 6 cases from 5 unrelated consanguineous families (2nd & 3rd degree) with homozygous LoF variants and a neurodevelopmental condition, including ID and seizures. Epb41l3 shRNA-mediated downregulation in mouse oligodendroglia demonstrated impaired oligodendrocyte function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6299 GCH1 Bryony Thompson Marked gene: GCH1 as ready
Intellectual disability syndromic and non-syndromic v0.6299 GCH1 Bryony Thompson Gene: gch1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6299 GCH1 Bryony Thompson Phenotypes for gene: GCH1 were changed from to GTP cyclohydrolase I deficiency with hyperphenylalaninemia MONDO:0100186
Intellectual disability syndromic and non-syndromic v0.6298 GCH1 Bryony Thompson Publications for gene: GCH1 were set to 22473768; 7869202
Intellectual disability syndromic and non-syndromic v0.6297 GCH1 Bryony Thompson Publications for gene: GCH1 were set to
Intellectual disability syndromic and non-syndromic v0.6296 GCH1 Bryony Thompson Mode of inheritance for gene: GCH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6295 GCH1 Bryony Thompson reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22473768, 7869202; Phenotypes: GTP cyclohydrolase I deficiency with hyperphenylalaninemia MONDO:0100186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6295 GAMT Bryony Thompson Marked gene: GAMT as ready
Intellectual disability syndromic and non-syndromic v0.6295 GAMT Bryony Thompson Gene: gamt has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6295 GAMT Bryony Thompson Phenotypes for gene: GAMT were changed from to guanidinoacetate methyltransferase deficiency MONDO:0012999
Intellectual disability syndromic and non-syndromic v0.6294 GAMT Bryony Thompson Publications for gene: GAMT were set to
Intellectual disability syndromic and non-syndromic v0.6293 GAMT Bryony Thompson Mode of inheritance for gene: GAMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6292 GAMT Bryony Thompson reviewed gene: GAMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301745; Phenotypes: guanidinoacetate methyltransferase deficiency MONDO:0012999; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6292 GALE Bryony Thompson Marked gene: GALE as ready
Intellectual disability syndromic and non-syndromic v0.6292 GALE Bryony Thompson Gene: gale has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6292 GALE Bryony Thompson Phenotypes for gene: GALE were changed from to galactose epimerase deficiency MONDO:0009257
Intellectual disability syndromic and non-syndromic v0.6291 GALE Bryony Thompson Publications for gene: GALE were set to
Intellectual disability syndromic and non-syndromic v0.6290 GALE Bryony Thompson Mode of inheritance for gene: GALE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6289 GALE Bryony Thompson reviewed gene: GALE: Rating: GREEN; Mode of pathogenicity: None; Publications: 21290786; Phenotypes: galactose epimerase deficiency MONDO:0009257; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6289 GALC Bryony Thompson Marked gene: GALC as ready
Intellectual disability syndromic and non-syndromic v0.6289 GALC Bryony Thompson Gene: galc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6289 GALC Bryony Thompson Phenotypes for gene: GALC were changed from to Krabbe disease MONDO:000949
Intellectual disability syndromic and non-syndromic v0.6288 GALC Bryony Thompson Publications for gene: GALC were set to
Intellectual disability syndromic and non-syndromic v0.6287 GALC Bryony Thompson Mode of inheritance for gene: GALC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6286 GALC Bryony Thompson reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301416; Phenotypes: Krabbe disease MONDO:000949; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6286 GABRB2 Bryony Thompson Marked gene: GABRB2 as ready
Intellectual disability syndromic and non-syndromic v0.6286 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6286 GABRB2 Bryony Thompson Phenotypes for gene: GABRB2 were changed from to epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631
Intellectual disability syndromic and non-syndromic v0.6285 GABRB2 Bryony Thompson Publications for gene: GABRB2 were set to
Intellectual disability syndromic and non-syndromic v0.6284 GABRB2 Bryony Thompson Mode of inheritance for gene: GABRB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6283 GABRB2 Bryony Thompson reviewed gene: GABRB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38996765; Phenotypes: epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6283 FUCA1 Bryony Thompson Marked gene: FUCA1 as ready
Intellectual disability syndromic and non-syndromic v0.6283 FUCA1 Bryony Thompson Gene: fuca1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6283 FUCA1 Bryony Thompson Phenotypes for gene: FUCA1 were changed from to Fucosidosis MONDO:0009254
Intellectual disability syndromic and non-syndromic v0.6282 FUCA1 Bryony Thompson Publications for gene: FUCA1 were set to
Intellectual disability syndromic and non-syndromic v0.6281 FUCA1 Bryony Thompson Mode of inheritance for gene: FUCA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6280 FUCA1 Bryony Thompson reviewed gene: FUCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33266441; Phenotypes: Fucosidosis MONDO:0009254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6280 FOXRED1 Bryony Thompson Marked gene: FOXRED1 as ready
Intellectual disability syndromic and non-syndromic v0.6280 FOXRED1 Bryony Thompson Gene: foxred1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6280 FOXRED1 Bryony Thompson Phenotypes for gene: FOXRED1 were changed from to Mitochondrial disease MONDO:0044970
Intellectual disability syndromic and non-syndromic v0.6279 FOXRED1 Bryony Thompson Publications for gene: FOXRED1 were set to
Intellectual disability syndromic and non-syndromic v0.6278 FOXRED1 Bryony Thompson Mode of inheritance for gene: FOXRED1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6277 FOXRED1 Bryony Thompson reviewed gene: FOXRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31434271, 20818383, 20858599; Phenotypes: Mitochondrial disease MONDO:0044970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6277 FOXG1 Bryony Thompson Marked gene: FOXG1 as ready
Intellectual disability syndromic and non-syndromic v0.6277 FOXG1 Bryony Thompson Gene: foxg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6277 FOXG1 Bryony Thompson Phenotypes for gene: FOXG1 were changed from to FOXG1 disorder MONDO:0100040
Intellectual disability syndromic and non-syndromic v0.6276 FOXG1 Bryony Thompson Publications for gene: FOXG1 were set to
Intellectual disability syndromic and non-syndromic v0.6275 FOXG1 Bryony Thompson Mode of inheritance for gene: FOXG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6274 FOXG1 Bryony Thompson reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18571142, 19578037, 19564653, 28661489; Phenotypes: FOXG1 disorder MONDO:0100040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6274 FKTN Bryony Thompson Marked gene: FKTN as ready
Intellectual disability syndromic and non-syndromic v0.6274 FKTN Bryony Thompson Gene: fktn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6274 FKTN Bryony Thompson Phenotypes for gene: FKTN were changed from to Myopathy caused by variation in FKTN MONDO:0700067
Intellectual disability syndromic and non-syndromic v0.6273 FKTN Bryony Thompson Publications for gene: FKTN were set to
Intellectual disability syndromic and non-syndromic v0.6272 FKTN Bryony Thompson Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6271 FKTN Bryony Thompson reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301385; Phenotypes: Myopathy caused by variation in FKTN MONDO:0700067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6271 FKRP Bryony Thompson Marked gene: FKRP as ready
Intellectual disability syndromic and non-syndromic v0.6271 FKRP Bryony Thompson Gene: fkrp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6271 FKRP Bryony Thompson Phenotypes for gene: FKRP were changed from myopathy caused by variation in FKRP MONDO:0700066 to myopathy caused by variation in FKRP MONDO:0700066
Intellectual disability syndromic and non-syndromic v0.6270 FKRP Bryony Thompson Phenotypes for gene: FKRP were changed from to myopathy caused by variation in FKRP MONDO:0700066
Intellectual disability syndromic and non-syndromic v0.6269 FKRP Bryony Thompson Publications for gene: FKRP were set to
Intellectual disability syndromic and non-syndromic v0.6268 FKRP Bryony Thompson Mode of inheritance for gene: FKRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6267 FKRP Bryony Thompson reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33200426, 11053680, 12654965, 14652796, 15121789; Phenotypes: myopathy caused by variation in FKRP MONDO:0700066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6267 FIG4 Bryony Thompson Marked gene: FIG4 as ready
Intellectual disability syndromic and non-syndromic v0.6267 FIG4 Bryony Thompson Gene: fig4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6267 FIG4 Bryony Thompson Phenotypes for gene: FIG4 were changed from to Charcot-Marie-Tooth disease MONDO:0015626
Intellectual disability syndromic and non-syndromic v0.6266 FIG4 Bryony Thompson Publications for gene: FIG4 were set to
Intellectual disability syndromic and non-syndromic v0.6265 FIG4 Bryony Thompson Mode of inheritance for gene: FIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6264 FIG4 Bryony Thompson reviewed gene: FIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 32385905, 34122524, 36529678; Phenotypes: Charcot-Marie-Tooth disease MONDO:0015626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6264 FBXL4 Bryony Thompson Marked gene: FBXL4 as ready
Intellectual disability syndromic and non-syndromic v0.6264 FBXL4 Bryony Thompson Gene: fbxl4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6264 FBXL4 Bryony Thompson Phenotypes for gene: FBXL4 were changed from to Leigh syndrome MONDO:0009723
Intellectual disability syndromic and non-syndromic v0.6263 FBXL4 Bryony Thompson Publications for gene: FBXL4 were set to
Intellectual disability syndromic and non-syndromic v0.6262 FBXL4 Bryony Thompson reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28383868; Phenotypes: Leigh syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6262 FBXL4 Bryony Thompson Mode of inheritance for gene: FBXL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6261 FAT4 Bryony Thompson Marked gene: FAT4 as ready
Intellectual disability syndromic and non-syndromic v0.6261 FAT4 Bryony Thompson Gene: fat4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6261 FAT4 Bryony Thompson Phenotypes for gene: FAT4 were changed from to Hennekam syndrome MONDO:0016256; van Maldergem syndrome MONDO:0017813
Intellectual disability syndromic and non-syndromic v0.6260 FAT4 Bryony Thompson Publications for gene: FAT4 were set to
Intellectual disability syndromic and non-syndromic v0.6259 FAT4 Bryony Thompson Mode of inheritance for gene: FAT4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6258 FAT4 Bryony Thompson reviewed gene: FAT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681106; Phenotypes: Hennekam syndrome MONDO:0016256, van Maldergem syndrome MONDO:0017813; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6258 FAM20C Bryony Thompson Marked gene: FAM20C as ready
Intellectual disability syndromic and non-syndromic v0.6258 FAM20C Bryony Thompson Gene: fam20c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6258 FAM20C Bryony Thompson Phenotypes for gene: FAM20C were changed from to lethal osteosclerotic bone dysplasia MONDO:0009821
Intellectual disability syndromic and non-syndromic v0.6257 FAM20C Bryony Thompson Publications for gene: FAM20C were set to
Intellectual disability syndromic and non-syndromic v0.6256 FAM20C Bryony Thompson Mode of inheritance for gene: FAM20C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6255 FAM20C Bryony Thompson reviewed gene: FAM20C: Rating: GREEN; Mode of pathogenicity: None; Publications: 34360805; Phenotypes: lethal osteosclerotic bone dysplasia MONDO:0009821; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6255 FAM126A Bryony Thompson Marked gene: FAM126A as ready
Intellectual disability syndromic and non-syndromic v0.6255 FAM126A Bryony Thompson Gene: fam126a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6255 FAM126A Bryony Thompson Phenotypes for gene: FAM126A were changed from to hypomyelinating leukodystrophy 5 MONDO:0012514
Intellectual disability syndromic and non-syndromic v0.6254 FAM126A Bryony Thompson Publications for gene: FAM126A were set to
Intellectual disability syndromic and non-syndromic v0.6253 FAM126A Bryony Thompson Mode of inheritance for gene: FAM126A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6252 FAM126A Bryony Thompson reviewed gene: FAM126A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301737; Phenotypes: hypomyelinating leukodystrophy 5 MONDO:0012514; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6252 ESCO2 Bryony Thompson Marked gene: ESCO2 as ready
Intellectual disability syndromic and non-syndromic v0.6252 ESCO2 Bryony Thompson Gene: esco2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6252 ESCO2 Bryony Thompson Phenotypes for gene: ESCO2 were changed from to Roberts-SC phocomelia syndrome MONDO:0100253
Intellectual disability syndromic and non-syndromic v0.6251 ESCO2 Bryony Thompson Publications for gene: ESCO2 were set to
Intellectual disability syndromic and non-syndromic v0.6250 ESCO2 Bryony Thompson Mode of inheritance for gene: ESCO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6249 ESCO2 Bryony Thompson reviewed gene: ESCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301332; Phenotypes: Roberts-SC phocomelia syndrome MONDO:0100253; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6249 INPP5K Sangavi Sivagnanasundram reviewed gene: INPP5K: Rating: GREEN; Mode of pathogenicity: None; Publications: 28190456, 28190459; Phenotypes: congenital muscular dystrophy with cataracts and intellectual disability MONDO:0024607; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6249 IKBKG Sangavi Sivagnanasundram reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301645; Phenotypes: Incontinentia pigmenti MONDO:0010631; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6249 RAF1 Chirag Patel reviewed gene: RAF1: 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: 17603483, 17603482, 31145547, 31030682, 29271604; Phenotypes: Noonan syndrome 5, MIM# 611553; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6249 RIT1 Chirag Patel reviewed gene: RIT1: 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: 23791108, 25124994, 24939608, 27101134; Phenotypes: Noonan syndrome 8, MIM# 615355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6249 RRAS2 Chirag Patel Classified gene: RRAS2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6249 RRAS2 Chirag Patel Gene: rras2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6248 RRAS2 Chirag Patel reviewed gene: RRAS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.6248 PTPN11 Chirag Patel reviewed gene: PTPN11: 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: 11992261,21533187, 24935154; Phenotypes: LEOPARD syndrome 1, 151100 AD (for reporting use Noonan syndrome with multiple lentigines), Metachondromatosis, 156250 AD, Noonan syndrome 1, 163950 AD, Leukemia, juvenile myelomonocytic, somatic, 607785; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6248 KRAS Chirag Patel reviewed gene: KRAS: 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: 21797849, 16474404, 16474405, 16773572, 17056636; Phenotypes: Noonan syndrome 3, MIM# 609942, Cardiofaciocutaneous syndrome 2, MIM# 615278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6248 NRAS Chirag Patel reviewed gene: NRAS: 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: 19966803, 26467218, 28594414; Phenotypes: Noonan syndrome 6, MIM# 613224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6248 NPHP1 Chirag Patel reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15138899, 32139166, 28347285, 8852662, 9856524; Phenotypes: Joubert syndrome 4, MIM# 609583, Nephronophthisis 1, juvenile, MIM# 256100, Senior-Loken syndrome-1, MIM# 266900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.6248 OTX2 Chirag Patel reviewed gene: OTX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24167467, 25589041, 31969185,; Phenotypes: Microphthalmia, syndromic 5, MIM# 610125, Pituitary hormone deficiency, combined, 6, MIM# 613986, Retinal dystrophy, early-onset, with or without pituitary dysfunction, MIM# 610125, Otocephaly-dysgnathia complex; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6248 OPA3 Chirag Patel reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25159689, 31119193, 31928268; Phenotypes: 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR, Optic atrophy 3 with cataract (MIM#165300), AD; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6248 OCLN Chirag Patel reviewed gene: OCLN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20727516, 32240828, 29192239, 28386946; Phenotypes: Pseudo-TORCH syndrome 1, MIM#251290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6248 ERCC8 Bryony Thompson Marked gene: ERCC8 as ready
Intellectual disability syndromic and non-syndromic v0.6248 ERCC8 Bryony Thompson Gene: ercc8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6248 ERCC8 Bryony Thompson Phenotypes for gene: ERCC8 were changed from to Cockayne syndrome type 1 MONDO:0019569
Intellectual disability syndromic and non-syndromic v0.6247 ERCC8 Bryony Thompson Publications for gene: ERCC8 were set to
Intellectual disability syndromic and non-syndromic v0.6246 ERCC8 Bryony Thompson Mode of inheritance for gene: ERCC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6245 ERCC8 Bryony Thompson reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301516; Phenotypes: Cockayne syndrome type 1 MONDO:0019569; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6245 ERCC6L2 Bryony Thompson Marked gene: ERCC6L2 as ready
Intellectual disability syndromic and non-syndromic v0.6245 ERCC6L2 Bryony Thompson Gene: ercc6l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6245 ERCC6L2 Bryony Thompson Phenotypes for gene: ERCC6L2 were changed from to pancytopenia-developmental delay syndrome MONDO:0014317
Intellectual disability syndromic and non-syndromic v0.6244 ERCC6L2 Bryony Thompson Publications for gene: ERCC6L2 were set to
Intellectual disability syndromic and non-syndromic v0.6243 ERCC6L2 Bryony Thompson Mode of inheritance for gene: ERCC6L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6242 ERCC6L2 Bryony Thompson reviewed gene: ERCC6L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36790458; Phenotypes: pancytopenia-developmental delay syndrome MONDO:0014317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6242 ERCC6 Bryony Thompson Marked gene: ERCC6 as ready
Intellectual disability syndromic and non-syndromic v0.6242 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6242 ERCC6 Bryony Thompson Phenotypes for gene: ERCC6 were changed from to Cockayne spectrum with or without cerebrooculofacioskeletal syndrome MONDO:0100506
Intellectual disability syndromic and non-syndromic v0.6241 ERCC6 Bryony Thompson Publications for gene: ERCC6 were set to
Intellectual disability syndromic and non-syndromic v0.6240 ERCC6 Bryony Thompson Mode of inheritance for gene: ERCC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6239 ERCC3 Bryony Thompson Marked gene: ERCC3 as ready
Intellectual disability syndromic and non-syndromic v0.6239 ERCC3 Bryony Thompson Gene: ercc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6239 ERCC3 Bryony Thompson Phenotypes for gene: ERCC3 were changed from to xeroderma pigmentosum group B MONDO:0012531
Intellectual disability syndromic and non-syndromic v0.6238 ERCC3 Bryony Thompson Publications for gene: ERCC3 were set to
Intellectual disability syndromic and non-syndromic v0.6237 ERCC3 Bryony Thompson Mode of inheritance for gene: ERCC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6236 ERCC2 Bryony Thompson Phenotypes for gene: ERCC2 were changed from xeroderma pigmentosum group D MONDO:0010212 to xeroderma pigmentosum group D MONDO:0010212; trichothiodystrophy 1, photosensitive MONDO:0011125; cerebrooculofacioskeletal syndrome 2 MONDO:0012553
Intellectual disability syndromic and non-syndromic v0.6235 ERCC2 Bryony Thompson Marked gene: ERCC2 as ready
Intellectual disability syndromic and non-syndromic v0.6235 ERCC2 Bryony Thompson Gene: ercc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6235 ERCC2 Bryony Thompson Phenotypes for gene: ERCC2 were changed from to xeroderma pigmentosum group D MONDO:0010212
Intellectual disability syndromic and non-syndromic v0.6234 ERCC2 Bryony Thompson Publications for gene: ERCC2 were set to
Intellectual disability syndromic and non-syndromic v0.6233 ERCC2 Bryony Thompson Mode of inheritance for gene: ERCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6232 EP300 Bryony Thompson Marked gene: EP300 as ready
Intellectual disability syndromic and non-syndromic v0.6232 EP300 Bryony Thompson Gene: ep300 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6232 EP300 Bryony Thompson Phenotypes for gene: EP300 were changed from to Rubinstein-Taybi syndrome MONDO:0019188
Intellectual disability syndromic and non-syndromic v0.6231 EP300 Bryony Thompson Publications for gene: EP300 were set to https://search.clinicalgenome.org/CCID:004751
Intellectual disability syndromic and non-syndromic v0.6230 EP300 Bryony Thompson Publications for gene: EP300 were set to
Intellectual disability syndromic and non-syndromic v0.6229 EP300 Bryony Thompson Mode of inheritance for gene: EP300 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6228 ELOVL4 Bryony Thompson Marked gene: ELOVL4 as ready
Intellectual disability syndromic and non-syndromic v0.6228 ELOVL4 Bryony Thompson Gene: elovl4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6228 ELOVL4 Bryony Thompson Phenotypes for gene: ELOVL4 were changed from to congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760
Intellectual disability syndromic and non-syndromic v0.6227 ELOVL4 Bryony Thompson Publications for gene: ELOVL4 were set to
Intellectual disability syndromic and non-syndromic v0.6226 ELOVL4 Bryony Thompson Mode of inheritance for gene: ELOVL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6225 EIF2AK3 Bryony Thompson Marked gene: EIF2AK3 as ready
Intellectual disability syndromic and non-syndromic v0.6225 EIF2AK3 Bryony Thompson Gene: eif2ak3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6225 EIF2AK3 Bryony Thompson Mode of inheritance for gene: EIF2AK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6224 EIF2AK3 Bryony Thompson Publications for gene: EIF2AK3 were set to
Intellectual disability syndromic and non-syndromic v0.6223 DIAPH1 Bryony Thompson Publications for gene: DIAPH1 were set to 24781755; 26463574
Intellectual disability syndromic and non-syndromic v0.6222 DIAPH1 Bryony Thompson reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39076976, 24781755, 26463574, 33662367; Phenotypes: progressive microcephaly-seizures-cortical blindness-developmental delay syndrome MONDO:0014714; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 ERCC6L2 Ken Lee Wan reviewed gene: ERCC6L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24507776, 27185855, 28815563, 29633571; Phenotypes: pancytopenia-developmental delay syndrome MONDO:0014317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 ERCC3 Ken Lee Wan reviewed gene: ERCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301571; Phenotypes: xeroderma pigmentosum group B MONDO:0012531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 ERCC2 Ken Lee Wan reviewed gene: ERCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301571; Phenotypes: xeroderma pigmentosum group D MONDO:0010212, trichothiodystrophy 1, photosensitive MONDO:0011125, cerebrooculofacioskeletal syndrome 2 MONDO:0012553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 EP300 Ken Lee Wan changed review comment from: EP300 is definitively associated with autosomal dominant Rubinstein-Taybi syndrome. Rubinstein-Taybi syndrome is characterized by distinctive facial features, broad and angulated thumbs and halluces, short stature, and intellectual disability (https://search.clinicalgenome.org/CCID:004751).

Mechanism of disease: loss of function; to: EP300 is definitively associated with autosomal dominant Rubinstein-Taybi syndrome. Rubinstein-Taybi syndrome is characterized by distinctive facial features, broad and angulated thumbs and halluces, short stature and intellectual disability (https://search.clinicalgenome.org/CCID:004751).

Mechanism of disease: loss of function
Intellectual disability syndromic and non-syndromic v0.6222 EP300 Ken Lee Wan reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rubinstein-Taybi syndrome MONDO:0019188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 ELOVL4 Ken Lee Wan reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 37592902; Phenotypes: congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 IFT172 Sangavi Sivagnanasundram reviewed gene: IFT172: Rating: AMBER; Mode of pathogenicity: None; Publications: 24290075, 26763875; Phenotypes: Bardet-Biedl syndrome MONDO:0015229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 IFIH1 Sangavi Sivagnanasundram changed review comment from: ID is a prominent feature of this condition in most cases and those affected will likely have severe intellectual and physical disability.

GoF is the mechanism of disease.; to: ID is a prominent feature of this condition in most cases and those affected will likely have severe intellectual and physical disability.

GoF is the mechanism of disease.

Classified as DEFINITIVE by ClinGen's Leukodystrophy and Leukoencephalopathy GCEP on 23/08/2024 - https://search.clinicalgenome.org/CCID:008354
Intellectual disability syndromic and non-syndromic v0.6222 IFIH1 Sangavi Sivagnanasundram reviewed gene: IFIH1: 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: 20301648, 25620204; Phenotypes: IFIH1-related type 1 interferonopathy MONDO:0700262; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6222 ERCC6 Mark Cleghorn reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301516; Phenotypes: Cockayne syndrome type B, Cerebrooculofacioskeletal syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 IDUA Sangavi Sivagnanasundram reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301341; Phenotypes: mucopolysaccharidosis type 1 MONDO:0001586; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 IDH2 Sangavi Sivagnanasundram reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20847235, 35359529; Phenotypes: mitochondrial disease MONDO:0044970; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.6222 HTRA2 Sangavi Sivagnanasundram reviewed gene: HTRA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27208207, 27696117, 30114719, 32445293; Phenotypes: 3-methylglutaconic aciduria type 8 MONDO:0044723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HSPD1 Sangavi Sivagnanasundram reviewed gene: HSPD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18571143, 27405012; Phenotypes: Leukodystrophy, hypomyelinating, 4, MIM #612233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HSD17B10 Sangavi Sivagnanasundram reviewed gene: HSD17B10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22132097, 17618155; Phenotypes: HSD10 mitochondrial disease MONDO:0010327; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6222 HPD Sangavi Sivagnanasundram reviewed gene: HPD: Rating: AMBER; Mode of pathogenicity: None; Publications: 31537781; Phenotypes: tyrosinemia type III MONDO:0010162; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HMGCL Sangavi Sivagnanasundram reviewed gene: HMGCL: Rating: AMBER; Mode of pathogenicity: None; Publications: 36771238, 35646072; Phenotypes: 3-hydroxy-3-methylglutaric aciduria MONDO:0009520; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HLCS Sangavi Sivagnanasundram reviewed gene: HLCS: Rating: GREEN; Mode of pathogenicity: None; Publications: 18974016, 18429047, 12124727; Phenotypes: holocarboxylase synthetase deficiency MONDO:0009666; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HIBCH Sangavi Sivagnanasundram reviewed gene: HIBCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24299452, 30847210, 17160907, 26163321, 26026795, 31523596, 32022391, 24299452, 32677093; Phenotypes: 3-hydroxyisobutyryl-CoA hydrolase deficiency MONDO:0009603, Leigh syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HEXB Sangavi Sivagnanasundram reviewed gene: HEXB: Rating: GREEN; Mode of pathogenicity: None; Publications: 35420740; Phenotypes: Sandhoff disease MONDO:0010006; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HEXA Sangavi Sivagnanasundram reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301397; Phenotypes: Tay-Sachs disease MONDO:0010100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HESX1 Sangavi Sivagnanasundram reviewed gene: HESX1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19623216, 30888394; Phenotypes: septooptic dysplasia MONDO:0008428, Pituitary hormone deficiency, combined, 5 MONDO:0013099; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HEPACAM Sangavi Sivagnanasundram reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 21419380, 24202401, 27389245, 31372844, 21419380, 24202401, 27322623; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 2A MONDO:0013490, Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability MONDO:0013491; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HCCS Sangavi Sivagnanasundram reviewed gene: HCCS: Rating: AMBER; Mode of pathogenicity: None; Publications: 18950397; Phenotypes: linear skin defects with multiple congenital anomalies 1 (MONDO:0024552); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6222 HADHA Sangavi Sivagnanasundram reviewed gene: HADHA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36063482; Phenotypes: long chain 3-hydroxyacyl-CoA dehydrogenase deficiency MONDO:0012173; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GTF2H5 Sangavi Sivagnanasundram reviewed gene: GTF2H5: Rating: AMBER; Mode of pathogenicity: None; Publications: 30359777, 24986372; Phenotypes: Trichothiodystrophy 3, photosensitive MIM#616395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GRM1 Sangavi Sivagnanasundram reviewed gene: GRM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26308914, 22901947, 31319223, 36675067; Phenotypes: autosomal recessive spinocerebellar ataxia 13 MONDO:0013905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GNS Sangavi Sivagnanasundram reviewed gene: GNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31536183, 25851924, 17998446, 6450420; Phenotypes: mucopolysaccharidosis type 3D MONDO:0009658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GNPTAB Sangavi Sivagnanasundram reviewed gene: GNPTAB: Rating: ; Mode of pathogenicity: None; Publications: 20301728; Phenotypes: GNPTAB-mucolipidosis MONDO:0100122; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GNPAT Sangavi Sivagnanasundram reviewed gene: GNPAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843043, 19270340, 21990100; Phenotypes: glyceronephosphate O-acyltransferase deficiency MONDO:0100273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GMPPB Sangavi Sivagnanasundram reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23768512, 26133662, 27147698; Phenotypes: myopathy caused by variation in GMPPB MONDO:0700084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GMPPA Sangavi Sivagnanasundram reviewed gene: GMPPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31898852, 35607266; Phenotypes: alacrima, achalasia, and intellectual disability syndrome MONDO:0014219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GM2A Sangavi Sivagnanasundram reviewed gene: GM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33819415, 20301397; Phenotypes: Tay-Sachs disease AB variant MONDO:0010099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Intellectual disability syndromic and non-syndromic v0.6222 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6222 DIAPH1 Zornitza Stark Phenotypes for gene: DIAPH1 were changed from to progressive microcephaly-seizures-cortical blindness-developmental delay syndrome MONDO:0014714
Intellectual disability syndromic and non-syndromic v0.6221 DIAPH1 Zornitza Stark Publications for gene: DIAPH1 were set to 24781755; 26463574
Intellectual disability syndromic and non-syndromic v0.6220 DIAPH1 Zornitza Stark Publications for gene: DIAPH1 were set to
Intellectual disability syndromic and non-syndromic v0.6220 DIAPH1 Zornitza Stark Mode of inheritance for gene: DIAPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6219 DIAPH1 Zornitza Stark reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: progressive microcephaly-seizures-cortical blindness-developmental delay syndrome MONDO:0014714; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6219 EIF2AK3 Ken Lee Wan reviewed gene: EIF2AK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20202148; Phenotypes: Wolcott-Rallison syndrome MONDO:0009192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6219 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Intellectual disability syndromic and non-syndromic v0.6219 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6219 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from to dyneinopathy MONDO:1040031
Intellectual disability syndromic and non-syndromic v0.6218 DYNC1H1 Zornitza Stark Mode of inheritance for gene: DYNC1H1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6217 DYNC1H1 Ken Lee Wan changed review comment from: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT) and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112); to: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT) and less frequently, intellectual disability and autism.

Mechanism of disease: gain of function
(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112)
Intellectual disability syndromic and non-syndromic v0.6217 DIS3L2 Zornitza Stark Marked gene: DIS3L2 as ready
Intellectual disability syndromic and non-syndromic v0.6217 DIS3L2 Zornitza Stark Gene: dis3l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6217 DIS3L2 Zornitza Stark Phenotypes for gene: DIS3L2 were changed from to Perlman syndrome MONDO:0009965
Intellectual disability syndromic and non-syndromic v0.6216 DIS3L2 Zornitza Stark Publications for gene: DIS3L2 were set to
Intellectual disability syndromic and non-syndromic v0.6215 DIAPH1 Ken Lee Wan changed review comment from: Seizures, cortical blindness, and microcephaly syndrome (SCBMS) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development, and cortical blindness. Affected individuals also tend to show poor overall growth with short stature (MIM: 616632).

Biallelic loss-of-function DIAPH1 variants have been reported in 3 Middle Eastern consanguineous families with a unique syndrome of early onset seizures, progressive microcephaly, intellectual disability and severe visual impairment (PMIDs: 24781755; 26463574). Western blot analysis showed lack of the mDia1 protein for affected individuals (PMID: 24781755).; to: Seizures, cortical blindness, and microcephaly syndrome (SCBMS) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development and cortical blindness. Affected individuals also tend to show poor overall growth with short stature (MIM: 616632).

Biallelic loss-of-function DIAPH1 variants have been reported in 3 Middle Eastern consanguineous families with a unique syndrome of early onset seizures, progressive microcephaly, intellectual disability and severe visual impairment (PMIDs: 24781755; 26463574). Western blot analysis showed lack of the mDia1 protein for affected individuals (PMID: 24781755).
Intellectual disability syndromic and non-syndromic v0.6215 DIS3L2 Zornitza Stark Mode of inheritance for gene: DIS3L2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6214 DNMT3B Ken Lee Wan changed review comment from: DNMT3B is a well-established gene disease association with autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome 1 (https://search.clinicalgenome.org/CCID:004692).

Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disease characterized by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9, and 16 after phytohemagglutinin (PHA) stimulation of lymphocytes. The most frequent symptoms of the syndrome are facial dysmorphism, intellectual disability, recurrent and prolonged respiratory infections, infections of the skin and digestive system and variable immune deficiency with a constant decrease of IgA (MIM: 242860).

Mechanism of disease: loss of function; to: DNMT3B is a well-established gene disease association with autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome 1 (https://search.clinicalgenome.org/CCID:004692).

Immunodeficiency, centromeric instability and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disease characterized by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after phytohemagglutinin (PHA) stimulation of lymphocytes. The most frequent symptoms of the syndrome are facial dysmorphism, intellectual disability, recurrent and prolonged respiratory infections, infections of the skin and digestive system and variable immune deficiency with a constant decrease of IgA (MIM: 242860).

Mechanism of disease: loss of function
Intellectual disability syndromic and non-syndromic v0.6214 DYNC1H1 Ken Lee Wan changed review comment from: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT), and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112); to: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT) and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112)
Intellectual disability syndromic and non-syndromic v0.6214 DYNC1H1 Ken Lee Wan changed review comment from: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT), and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM#600112); to: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT), and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112)
Intellectual disability syndromic and non-syndromic v0.6214 DYNC1H1 Ken Lee Wan reviewed gene: DYNC1H1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: dyneinopathy MONDO:1040031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6214 DIS3L2 Zornitza Stark Mode of inheritance for gene: DIS3L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6213 DNAJC19 Zornitza Stark Marked gene: DNAJC19 as ready
Intellectual disability syndromic and non-syndromic v0.6213 DNAJC19 Zornitza Stark Gene: dnajc19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6213 DNAJC19 Zornitza Stark Phenotypes for gene: DNAJC19 were changed from 3-methylglutaconic aciduria type 5 MONDO:0012435 to 3-methylglutaconic aciduria type 5 MONDO:0012435
Intellectual disability syndromic and non-syndromic v0.6212 DNAJC19 Zornitza Stark Phenotypes for gene: DNAJC19 were changed from to 3-methylglutaconic aciduria type 5 MONDO:0012435
Intellectual disability syndromic and non-syndromic v0.6211 DNAJC19 Zornitza Stark Mode of inheritance for gene: DNAJC19 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6210 DNAJC19 Zornitza Stark Mode of inheritance for gene: DNAJC19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6209 DNMT3B Zornitza Stark Marked gene: DNMT3B as ready
Intellectual disability syndromic and non-syndromic v0.6209 DNMT3B Zornitza Stark Gene: dnmt3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6209 DNMT3B Zornitza Stark Phenotypes for gene: DNMT3B were changed from to immunodeficiency-centromeric instability-facial anomalies syndrome 1 MONDO:0009454
Intellectual disability syndromic and non-syndromic v0.6208 DNMT3B Zornitza Stark Mode of inheritance for gene: DNMT3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6207 DNMT3B Ken Lee Wan reviewed gene: DNMT3B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: immunodeficiency-centromeric instability-facial anomalies syndrome 1 MONDO:0009454; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6207 DNAJC19 Ken Lee Wan reviewed gene: DNAJC19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria type 5 MONDO:0012435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6207 DIS3L2 Ken Lee Wan changed review comment from: Perlman syndrome is a well-established gene-disease association with autosomal recessive Perlman syndrome (https://search.clinicalgenome.org/CCID:004649)

Perlman syndrome (PRLMNS) is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic and show organomegaly, characteristic facial dysmorphisms, renal anomalies, frequent neurodevelopmental delay and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumour (OMIM: 267000).

PMID 16278893: 6 out of 22 patients have developmental delay

PMID 22306653: 5 surviving patients with at least one loss-of-function variant identified have developmental delay.

PMID 28328139: 1 surviving patient with compound heterozygous (splice site and missense variants) has developmental delay

Mechanism of disease causation: loss of function; to: DIS3L2 is a well-established gene-disease association with autosomal recessive Perlman syndrome (https://search.clinicalgenome.org/CCID:004649)

Perlman syndrome (PRLMNS) is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic and show organomegaly, characteristic facial dysmorphisms, renal anomalies, frequent neurodevelopmental delay and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumour (OMIM: 267000).

PMID 16278893: 6 out of 22 patients have developmental delay

PMID 22306653: 5 surviving patients with at least one loss-of-function variant identified have developmental delay.

PMID 28328139: 1 surviving patient with compound heterozygous (splice site and missense variants) has developmental delay

Mechanism of disease causation: loss of function
Intellectual disability syndromic and non-syndromic v0.6207 DIS3L2 Ken Lee Wan reviewed gene: DIS3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16278893, 22306653, 28328139; Phenotypes: Perlman syndrome MONDO:0009965; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6207 DIAPH1 Ken Lee Wan reviewed gene: DIAPH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 24781755, 26463574; Phenotypes: progressive microcephaly-seizures-cortical blindness-developmental delay syndrome MONDO:0014714; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6207 RBSN Zornitza Stark Phenotypes for gene: RBSN were changed from intellectual disability, MONDO:0001071 to Kariminejad-Reversade neurodevelopmental syndrome, MIM# 620937
Intellectual disability syndromic and non-syndromic v0.6206 RBSN Zornitza Stark reviewed gene: RBSN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kariminejad-Reversade neurodevelopmental syndrome, MIM# 620937; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6206 RNU2-2P Zornitza Stark Marked gene: RNU2-2P as ready
Intellectual disability syndromic and non-syndromic v0.6206 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6206 RNU2-2P Zornitza Stark Classified gene: RNU2-2P as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6206 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6205 RNU2-2P Zornitza Stark gene: RNU2-2P was added
gene: RNU2-2P was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNU2-2P was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU2-2P were set to https://www.medrxiv.org/content/10.1101/2024.09.03.24312863v1
Phenotypes for gene: RNU2-2P were set to Neurodevelopmental disorder, MONDO:0700092, RNU2-2P-related
Review for gene: RNU2-2P was set to GREEN
Added comment: 15 individuals reported with de novo, recurrent variants in this gene at nucleotide positions 4 and 35. The disorder is characterized by intellectual disability, neurodevelopmental delay, autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases display a severe and complex seizure phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6204 REPS2 Bryony Thompson Marked gene: REPS2 as ready
Intellectual disability syndromic and non-syndromic v0.6204 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6204 REPS2 Bryony Thompson Classified gene: REPS2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6204 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6203 TTL Bryony Thompson Marked gene: TTL as ready
Intellectual disability syndromic and non-syndromic v0.6203 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6203 TTL Bryony Thompson Classified gene: TTL as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6203 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6202 GPN2 Bryony Thompson Marked gene: GPN2 as ready
Intellectual disability syndromic and non-syndromic v0.6202 GPN2 Bryony Thompson Gene: gpn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6202 GPN2 Bryony Thompson Classified gene: GPN2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6202 GPN2 Bryony Thompson Gene: gpn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6201 FKBP4 Bryony Thompson Marked gene: FKBP4 as ready
Intellectual disability syndromic and non-syndromic v0.6201 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6201 FKBP4 Bryony Thompson Classified gene: FKBP4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6201 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6200 EIF3I Bryony Thompson Marked gene: EIF3I as ready
Intellectual disability syndromic and non-syndromic v0.6200 EIF3I Bryony Thompson Gene: eif3i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6200 EIF3I Bryony Thompson Classified gene: EIF3I as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6200 EIF3I Bryony Thompson Gene: eif3i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6199 EIF3I Bryony Thompson Classified gene: EIF3I as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6199 EIF3I Bryony Thompson Gene: eif3i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6198 CEP76 Bryony Thompson Marked gene: CEP76 as ready
Intellectual disability syndromic and non-syndromic v0.6198 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6198 CEP76 Bryony Thompson Classified gene: CEP76 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6198 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6197 MRAS Krithika Murali Mode of inheritance for gene: MRAS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6197 MRAS Krithika Murali Classified gene: MRAS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6197 MRAS Krithika Murali Gene: mras has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6196 MRAS Krithika Murali Marked gene: MRAS as ready
Intellectual disability syndromic and non-syndromic v0.6196 MRAS Krithika Murali Gene: mras has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6196 MRAS Krithika Murali gene: MRAS was added
gene: MRAS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MRAS were set to Noonan syndrome 11 - MIM#618499
Review for gene: MRAS was set to GREEN
Added comment: Developmental delay is a phenotypic feature
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6195 CEP76 Mark Cleghorn gene: CEP76 was added
gene: CEP76 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: CEP76 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP76 were set to complex neurodevelopmental disorder MONDO:0100038; Joubert syndrome; Bardet-Biedl syndrome; retinitis pigmentosa
Penetrance for gene: CEP76 were set to unknown
Review for gene: CEP76 was set to GREEN
Added comment: Erica Davis, Stanley Manne Children’s research institute, Chicago
ESHG presentation 4/6/24, unpublished

CEP76 associated with syndromic ciliopathy

CEP76 localizes to centrioles and basal body primary cilia
Role in normal centriolar duplication

Index case
Bardet Biedl syndrome
Compound heterozygous pLoF variants in CEP76

Via Gene matcher
7 cases in 7 families- biallelic CEP76 and various clinical features within ciliopathy spectrum:
Obesity
Ocular phenotype
Structural brain anomalies
Renal?

3/7 families clinical Dx Joubert syndrome
1/7 BBS
1/7 GDD/ID NOS
2/7 retinitis pigmentosa (1 of these with learning difficulties)

Mixture of biallelic pLOF and missense variant

CEP76 knockout zebrafish model shows retinal phenotype w photoreceptor loss, similar to homozygous known BBS4 pathogenic variant

Cell based fx studies with missense variants above, consistent with centriolar duplication dysfunction
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6195 EIF3I Mark Cleghorn gene: EIF3I was added
gene: EIF3I was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: EIF3I was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EIF3I were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: EIF3I were set to unknown
Review for gene: EIF3I was set to AMBER
Added comment: Marcello Scala, Genoa
ESHG presentation 4/6/24, unpublished

De novo EIF3I missense variants as a cause for novel NDD syndrome

EIF3 complex involved in regulating initiation of mRNA translation
Negative regulator of the TGF beta pathway

8 individuals from 8 families
Mod/severe GDD or ID
Short stature
Midline brain anomalies (hypoplasia/agenesis of corpus callosum and pituitary hypoplasia)
Frontal bossing, hypertelorism, long philtrum
All w rare de novo missense variants om EIF3I, clustering within highly conserved WD repeats

Functional studies
Transfected HEK293 cell studies suggested EIF3I protein from variant alleles (from patients above) had disrupted interaction with other EIF subunits, and cells had reduced protein synthesis overall
No animal models
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6195 DDHD2 Bryony Thompson Phenotypes for gene: DDHD2 were changed from hereditary spastic paraplegia 54 MONDO:0014018 to hereditary spastic paraplegia 54 MONDO:0014018
Intellectual disability syndromic and non-syndromic v0.6194 DDHD2 Bryony Thompson Marked gene: DDHD2 as ready
Intellectual disability syndromic and non-syndromic v0.6194 DDHD2 Bryony Thompson Gene: ddhd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6194 DDHD2 Bryony Thompson Phenotypes for gene: DDHD2 were changed from to hereditary spastic paraplegia 54 MONDO:0014018
Intellectual disability syndromic and non-syndromic v0.6193 DDHD2 Bryony Thompson Publications for gene: DDHD2 were set to
Intellectual disability syndromic and non-syndromic v0.6192 DDHD2 Bryony Thompson Mode of inheritance for gene: DDHD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6191 DDHD2 Bryony Thompson reviewed gene: DDHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23486545, 23176823, 36090575, 26113134, 25417924; Phenotypes: hereditary spastic paraplegia 54 MONDO:0014018; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6191 DDC Bryony Thompson Marked gene: DDC as ready
Intellectual disability syndromic and non-syndromic v0.6191 DDC Bryony Thompson Gene: ddc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6191 DDC Bryony Thompson Publications for gene: DDC were set to
Intellectual disability syndromic and non-syndromic v0.6190 DDC Bryony Thompson Mode of inheritance for gene: DDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6189 DDC Bryony Thompson reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 37824694; Phenotypes: Aromatic L-amino acid decarboxylase deficiency MONDO:0012084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6189 FKBP4 Mark Cleghorn gene: FKBP4 was added
gene: FKBP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: FKBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKBP4 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: FKBP4 were set to unknown
Review for gene: FKBP4 was set to AMBER
Added comment: Rebecca Yarwood, University of Manchester
ESHG presentation 4/6/24, unpublished

Bilalleic FKBP4 w NDD + DSD
Protein has functions in hormone receptor trafficking
FKPB4 highly expressed in stem cell and progenitor cells in gonad and neuronal degeneration

Index case
Severe GDD
abN external genitalia
CV AbN
FBBP4 p.E196*

Via GeneMatcher
7 families (12 individuals)

12/12 severe GDD/ID
9/10 microcephaly
11/12 external genital abnormalities (details not provided)

All w homozygous pLoF variants (mixture of canonical splice, frameshift, nonsense)
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6189 MED16 Bryony Thompson Classified gene: MED16 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6189 MED16 Bryony Thompson Gene: med16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6188 MED16 Mark Cleghorn gene: MED16 was added
gene: MED16 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: MED16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MED16 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: MED16 were set to unknown
Review for gene: MED16 was set to GREEN
Added comment: MED16
Charlotte Guillouet, Imagine institute Paris
ESHG presentation 4/6/24, unpublished

MED16 is part of tail of ‘mediator complex’
Plays a role in enhancer/promotor regions

Disruptive variants in other genes encoding proteins within this mediator complex (MED11/12/12/17/20, CDK8) are assoc w neurodevelopmental/neurodegenerative disorders

Cases
index family
Sibs (M/F) to consanguineous parents w NDD/mod ID, tetralogy of Fallot or VSD, bilat deafness, micrognathia, malar hypoplasia, dental AbN, pre auricular tags, hypoplastic nails, brachydactly
WES: biallelic MED16 p.Asp217Asn

Via genematcher
16 families total, 22 individuals, homozygous or compound het rare MED16 variants
Mixture of pLoF and missense variants

Motor delay in 16/17
DD or ID in 17/17
Speech delay in 15/15
6/19 ToF
7/19 other septal/aortic defects
6/18 deafness
11/18 microretognathia
6/17 cleft palate
8/19 preauricular tags
9/20 puffy eyelids
12/20 nasal dysplasia (most commonly short columella w bulbous nasal tip)
7/20 corpus callosum anomalies

Not clear that functional work recapitulated phenotype as yet?
Immunofluroescence on HeLa cells transfected with variants observed ?conclusion
MED16 knockout mouse > growth delay, pre weaning lethality
MED16 knockout zebrafish > reduced body length, early death, no obvious craniofacial phenotype
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6188 LARS2 Chirag Patel reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29205794, 32423379, 30737337, 26537577, 23541342; Phenotypes: Perrault syndrome 4, MIM# 615300, Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 LARGE1 Chirag Patel reviewed gene: LARGE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12966029, 19067344, 17436019, 21248746, 19299310; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM# 608840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 LAMP2 Chirag Patel reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 10972294; Phenotypes: Danon disease, MIM# 300257, MONDO:0010281; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 PARN Chirag Patel reviewed gene: PARN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25893599, 26342108; Phenotypes: Dyskeratosis congenita, autosomal recessive 6, MIM# 616353; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 PAX6 Chirag Patel reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 26130484, 31700164; Phenotypes: Microphthalmia/coloboma 12, OMIM #120200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6188 PAX8 Chirag Patel reviewed gene: PAX8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33272083, 9590296 11232006 15356023 15718293; Phenotypes: Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 PC Chirag Patel reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9585612, 12112657; Phenotypes: Pyruvate carboxylase deficiency - MIM#266150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 SLC6A3 Zornitza Stark Marked gene: SLC6A3 as ready
Intellectual disability syndromic and non-syndromic v0.6188 SLC6A3 Zornitza Stark Gene: slc6a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6188 SLC6A3 Zornitza Stark Phenotypes for gene: SLC6A3 were changed from to Parkinsonism-dystonia, infantile, 1, MIM# 613135
Intellectual disability syndromic and non-syndromic v0.6187 SLC6A3 Zornitza Stark Publications for gene: SLC6A3 were set to
Intellectual disability syndromic and non-syndromic v0.6186 SLC6A3 Zornitza Stark Mode of inheritance for gene: SLC6A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6185 SLC6A3 Zornitza Stark reviewed gene: SLC6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21112253; Phenotypes: Parkinsonism-dystonia, infantile, 1, MIM# 613135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6185 SRD5A3 Zornitza Stark Marked gene: SRD5A3 as ready
Intellectual disability syndromic and non-syndromic v0.6185 SRD5A3 Zornitza Stark Gene: srd5a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6185 SRD5A3 Zornitza Stark Phenotypes for gene: SRD5A3 were changed from to Congenital disorder of glycosylation, type Iq, MIM#612379; Kahrizi syndrome, MIM# 612713
Intellectual disability syndromic and non-syndromic v0.6184 SRD5A3 Zornitza Stark Publications for gene: SRD5A3 were set to
Intellectual disability syndromic and non-syndromic v0.6183 SRD5A3 Zornitza Stark Mode of inheritance for gene: SRD5A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6182 SRD5A3 Zornitza Stark reviewed gene: SRD5A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32424323; Phenotypes: Congenital disorder of glycosylation, type Iq, MIM#612379, Kahrizi syndrome, MIM# 612713; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6182 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Intellectual disability syndromic and non-syndromic v0.6182 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6182 SLC6A8 Zornitza Stark Phenotypes for gene: SLC6A8 were changed from to Cerebral creatine deficiency syndrome 1, MIM# 300352
Intellectual disability syndromic and non-syndromic v0.6181 SLC6A8 Zornitza Stark Publications for gene: SLC6A8 were set to
Intellectual disability syndromic and non-syndromic v0.6180 SLC6A8 Zornitza Stark Mode of inheritance for gene: SLC6A8 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6179 SLC6A8 Zornitza Stark reviewed gene: SLC6A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 27604308, 16738945; Phenotypes: Cerebral creatine deficiency syndrome 1, MIM# 300352; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6179 SPTBN2 Zornitza Stark Mode of inheritance for gene: SPTBN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6178 SPTBN2 Zornitza Stark reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23236289, 23838597, 22781464, 31617442, 31066025; Phenotypes: Spinocerebellar ataxia, autosomal recessive 14, MIM# 615386, Spinocerebellar ataxia 5, MIM# 600224; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6178 ST3GAL3 Zornitza Stark Marked gene: ST3GAL3 as ready
Intellectual disability syndromic and non-syndromic v0.6178 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6178 ST3GAL3 Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from to Intellectual disability, autosomal recessive 12 MIM# 611090
Intellectual disability syndromic and non-syndromic v0.6177 ST3GAL3 Zornitza Stark Publications for gene: ST3GAL3 were set to
Intellectual disability syndromic and non-syndromic v0.6176 ST3GAL3 Zornitza Stark Mode of inheritance for gene: ST3GAL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6175 ST3GAL3 Zornitza Stark reviewed gene: ST3GAL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23252400, 21907012, 31584066, 37938134; Phenotypes: Intellectual disability, autosomal recessive 12 MIM# 611090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6175 SUCLG1 Zornitza Stark Marked gene: SUCLG1 as ready
Intellectual disability syndromic and non-syndromic v0.6175 SUCLG1 Zornitza Stark Gene: suclg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6175 SUCLG1 Zornitza Stark Phenotypes for gene: SUCLG1 were changed from Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400 to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400
Intellectual disability syndromic and non-syndromic v0.6174 SUCLG1 Zornitza Stark Phenotypes for gene: SUCLG1 were changed from to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400
Intellectual disability syndromic and non-syndromic v0.6173 SUCLG1 Zornitza Stark Publications for gene: SUCLG1 were set to
Intellectual disability syndromic and non-syndromic v0.6172 SUCLG1 Zornitza Stark Mode of inheritance for gene: SUCLG1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6171 SUCLG1 Zornitza Stark Mode of inheritance for gene: SUCLG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6170 SUCLG1 Zornitza Stark reviewed gene: SUCLG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33230783, 28358460; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6170 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Intellectual disability syndromic and non-syndromic v0.6170 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6170 SURF1 Zornitza Stark Phenotypes for gene: SURF1 were changed from to Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110
Intellectual disability syndromic and non-syndromic v0.6169 SURF1 Zornitza Stark Publications for gene: SURF1 were set to
Intellectual disability syndromic and non-syndromic v0.6168 SURF1 Zornitza Stark Mode of inheritance for gene: SURF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6167 SURF1 Zornitza Stark reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843204, 9837813; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6167 TMEM5 Zornitza Stark Tag new gene name tag was added to gene: TMEM5.
Intellectual disability syndromic and non-syndromic v0.6167 TMEM5 Zornitza Stark Marked gene: TMEM5 as ready
Intellectual disability syndromic and non-syndromic v0.6167 TMEM5 Zornitza Stark Gene: tmem5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6167 TMEM5 Zornitza Stark Phenotypes for gene: TMEM5 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, MIM# 615041
Intellectual disability syndromic and non-syndromic v0.6166 TMEM5 Zornitza Stark Publications for gene: TMEM5 were set to 23217329; 23519211
Intellectual disability syndromic and non-syndromic v0.6165 TMEM5 Zornitza Stark Publications for gene: TMEM5 were set to
Intellectual disability syndromic and non-syndromic v0.6164 TMEM5 Zornitza Stark Mode of inheritance for gene: TMEM5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6163 TMEM5 Zornitza Stark reviewed gene: TMEM5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23217329, 23519211; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, MIM# 615041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6163 TSEN2 Zornitza Stark Marked gene: TSEN2 as ready
Intellectual disability syndromic and non-syndromic v0.6163 TSEN2 Zornitza Stark Gene: tsen2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6163 TSEN2 Zornitza Stark Phenotypes for gene: TSEN2 were changed from to Pontocerebellar hypoplasia type 2B, MIM# 612389
Intellectual disability syndromic and non-syndromic v0.6162 TSEN2 Zornitza Stark Publications for gene: TSEN2 were set to 23562994; 20952379
Intellectual disability syndromic and non-syndromic v0.6161 TSEN2 Zornitza Stark Publications for gene: TSEN2 were set to
Intellectual disability syndromic and non-syndromic v0.6160 TSEN2 Zornitza Stark Mode of inheritance for gene: TSEN2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6159 TSEN2 Zornitza Stark Mode of inheritance for gene: TSEN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6158 TSEN2 Zornitza Stark reviewed gene: TSEN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23562994, 20952379; Phenotypes: Pontocerebellar hypoplasia type 2B, MIM# 612389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6158 TTC19 Zornitza Stark Marked gene: TTC19 as ready
Intellectual disability syndromic and non-syndromic v0.6158 TTC19 Zornitza Stark Gene: ttc19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6158 TTC19 Zornitza Stark Phenotypes for gene: TTC19 were changed from to Mitochondrial complex III deficiency, nuclear type 2, MIM#615157
Intellectual disability syndromic and non-syndromic v0.6157 TTC19 Zornitza Stark Publications for gene: TTC19 were set to
Intellectual disability syndromic and non-syndromic v0.6156 TTC19 Zornitza Stark Mode of inheritance for gene: TTC19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6155 TTC19 Zornitza Stark changed review comment from: Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life. The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances.

At least 4 unrelated families reported.; to: Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life. The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances.

Included due to phenotypic overlap.

At least 4 unrelated families reported.
Intellectual disability syndromic and non-syndromic v0.6155 TTC19 Zornitza Stark reviewed gene: TTC19: Rating: GREEN; Mode of pathogenicity: None; Publications: 21278747, 23532514, 24368687, 24397319; Phenotypes: Mitochondrial complex III deficiency, nuclear type 2, MIM#615157; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6155 TUBA1A Zornitza Stark Marked gene: TUBA1A as ready
Intellectual disability syndromic and non-syndromic v0.6155 TUBA1A Zornitza Stark Gene: tuba1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6155 TUBA1A Zornitza Stark Phenotypes for gene: TUBA1A were changed from to Lissencephaly 3, MIM# 611603
Intellectual disability syndromic and non-syndromic v0.6154 TUBA1A Zornitza Stark Mode of inheritance for gene: TUBA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6153 TUBA1A Zornitza Stark reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 3, MIM# 611603; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6153 ZNRF3 Bryony Thompson Marked gene: ZNRF3 as ready
Intellectual disability syndromic and non-syndromic v0.6153 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6153 ZNRF3 Bryony Thompson Classified gene: ZNRF3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6153 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6152 ZNRF3 Bryony Thompson gene: ZNRF3 was added
gene: ZNRF3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZNRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNRF3 were set to 39168120
Phenotypes for gene: ZNRF3 were set to Complex neurodevelopmental disorder MONDO:0100038
Review for gene: ZNRF3 was set to GREEN
Added comment: 12 individuals with ZNRF3 variants and various phenotypes. 8 individuals with de novo missense and neurodevelopment disorders (NDD), including cluster of variants in the RING ligase domain with macrocephalic NDD. Plus 4 individuals from 3 families with de novo truncating or de novo/inherited large in-frame deletion variants with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. Overall, 4 individuals had congenital heart defects and 2 had microcephaly. Also, supporting in vitro functional assays.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6151 NFIA Zornitza Stark Marked gene: NFIA as ready
Intellectual disability syndromic and non-syndromic v0.6151 NFIA Zornitza Stark Gene: nfia has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6151 DHTKD1 Zornitza Stark Marked gene: DHTKD1 as ready
Intellectual disability syndromic and non-syndromic v0.6151 DHTKD1 Zornitza Stark Gene: dhtkd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6151 DHTKD1 Zornitza Stark Phenotypes for gene: DHTKD1 were changed from to 2-aminoadipic 2-oxoadipic aciduria MIM#204750; Disorders of histidine, tryptophan or lysine metabolism
Intellectual disability syndromic and non-syndromic v0.6150 DHTKD1 Zornitza Stark Publications for gene: DHTKD1 were set to
Intellectual disability syndromic and non-syndromic v0.6149 DHTKD1 Zornitza Stark Mode of inheritance for gene: DHTKD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6148 DHTKD1 Zornitza Stark Classified gene: DHTKD1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6148 DHTKD1 Zornitza Stark Gene: dhtkd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6147 DCX Zornitza Stark Marked gene: DCX as ready
Intellectual disability syndromic and non-syndromic v0.6147 DCX Zornitza Stark Gene: dcx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6147 DCX Zornitza Stark Phenotypes for gene: DCX were changed from to Lissencephaly, X-linked, MIM# 300067; Subcortical laminal heterotopia, X-linked 300067
Intellectual disability syndromic and non-syndromic v0.6146 DCX Zornitza Stark Publications for gene: DCX were set to 26743950; 11468322; 20726879; 20301364; 12552055; 9489699
Intellectual disability syndromic and non-syndromic v0.6145 DCX Zornitza Stark Publications for gene: DCX were set to
Intellectual disability syndromic and non-syndromic v0.6144 DCX Zornitza Stark Mode of inheritance for gene: DCX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6143 DARS2 Zornitza Stark Marked gene: DARS2 as ready
Intellectual disability syndromic and non-syndromic v0.6143 DARS2 Zornitza Stark Gene: dars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6143 DARS2 Zornitza Stark Phenotypes for gene: DARS2 were changed from to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105
Intellectual disability syndromic and non-syndromic v0.6142 DARS2 Zornitza Stark Publications for gene: DARS2 were set to
Intellectual disability syndromic and non-syndromic v0.6141 DARS2 Zornitza Stark Mode of inheritance for gene: DARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6140 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Intellectual disability syndromic and non-syndromic v0.6140 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6140 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria MIM#600721
Intellectual disability syndromic and non-syndromic v0.6139 D2HGDH Zornitza Stark Publications for gene: D2HGDH were set to
Intellectual disability syndromic and non-syndromic v0.6138 D2HGDH Zornitza Stark Mode of inheritance for gene: D2HGDH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6137 D2HGDH Zornitza Stark Mode of inheritance for gene: D2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6136 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119 to Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119
Intellectual disability syndromic and non-syndromic v0.6136 COX15 Zornitza Stark Marked gene: COX15 as ready
Intellectual disability syndromic and non-syndromic v0.6136 COX15 Zornitza Stark Gene: cox15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6136 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119 to Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119
Intellectual disability syndromic and non-syndromic v0.6135 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from to Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119
Intellectual disability syndromic and non-syndromic v0.6134 GPN2 Mark Cleghorn gene: GPN2 was added
gene: GPN2 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: GPN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPN2 were set to complex neurodevelopmental disorder MONDO:0100038; Perrault syndrome
Review for gene: GPN2 was set to AMBER
Added comment: GPN2
ESHG talk 2/6/24, unpublished
Thomas Smith, University of Manchester

Biallelic GPN2 proposed to cause Perrault syndrome (SNHL, ovarian dysfunction, NDD)
RNA polymerase assembly factor

4 families (14 affected individuals) w biallalic GPN2 rare missense variants
Segregated w phenotype
Fam 2 and 3 may be distantly related (leaving 3 distinct kindreds)

Clinical features
13/14 SNHL
3/4 families all females of adolescent age or older had primary ovarian insufficiency
4/4 GDD, ataxia (no data on family w 10 affected indiv.)

Some functional work, not conclusive
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6134 ATP6V1C1 Zornitza Stark Marked gene: ATP6V1C1 as ready
Intellectual disability syndromic and non-syndromic v0.6134 ATP6V1C1 Zornitza Stark Gene: atp6v1c1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6134 ATP6V1C1 Zornitza Stark gene: ATP6V1C1 was added
gene: ATP6V1C1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATP6V1C1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V1C1 were set to 39210597
Phenotypes for gene: ATP6V1C1 were set to neurodevelopmental disorder MONDO:0700092, ATP6V1C1-related
Review for gene: ATP6V1C1 was set to RED
Added comment: 1x de novo missense p.Glu289Lys (absent in v4 gnomad). Manual inspection of IGV found the dad was mosaic 7% VAF and he shared some of the clinical features (minor digit anomalies). Some functional studies using patient fibroblasts were performed, demonstrating similar effects as known pathogenic variants in ATP6V1B2. - lysosomal morphology - autophagic flux dysregulation - increased acidification of lysosome borderline red/amber
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6133 C12orf66 Zornitza Stark Marked gene: C12orf66 as ready
Intellectual disability syndromic and non-syndromic v0.6133 C12orf66 Zornitza Stark Gene: c12orf66 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6133 C12orf66 Zornitza Stark Classified gene: C12orf66 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6133 C12orf66 Zornitza Stark Gene: c12orf66 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6132 SF3B1 Zornitza Stark Marked gene: SF3B1 as ready
Intellectual disability syndromic and non-syndromic v0.6132 SF3B1 Zornitza Stark Gene: sf3b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6132 SF3B1 Zornitza Stark Classified gene: SF3B1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6132 SF3B1 Zornitza Stark Gene: sf3b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6131 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6131 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6131 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6131 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6130 MED22 Zornitza Stark Marked gene: MED22 as ready
Intellectual disability syndromic and non-syndromic v0.6130 MED22 Zornitza Stark Gene: med22 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6130 MED22 Zornitza Stark Classified gene: MED22 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6130 MED22 Zornitza Stark Gene: med22 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6129 LARP1 Zornitza Stark Marked gene: LARP1 as ready
Intellectual disability syndromic and non-syndromic v0.6129 LARP1 Zornitza Stark Gene: larp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6129 LARP1 Zornitza Stark Classified gene: LARP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6129 LARP1 Zornitza Stark Gene: larp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6128 PNPLA8 Zornitza Stark Marked gene: PNPLA8 as ready
Intellectual disability syndromic and non-syndromic v0.6128 PNPLA8 Zornitza Stark Gene: pnpla8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6128 PNPLA8 Zornitza Stark Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases to Complex neurodevelopmental disorder, MONDO:0100038, PNPLA8-related
Intellectual disability syndromic and non-syndromic v0.6127 RFC4 Chirag Patel gene: RFC4 was added
gene: RFC4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to PMID: 39106866
Phenotypes for gene: RFC4 were set to RFC4-related multisystem disorder
Review for gene: RFC4 was set to GREEN
gene: RFC4 was marked as current diagnostic
Added comment: 9 affected individuals (aged birth to 47yrs) from 8 unrelated families with a multisystem disorder. Clinical features included: muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

WES or WGS identified biallelic loss-of-function variants in RFC4 (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions, 2 missense), and almost all are likely to disrupt the C-terminal domain indispensable for Replication factor C (RFC) complex formation. All variants segregated with the disease.

The RFC complex (with 5 subunits) is central to process of regulation of DNA replication, and it loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. RFC1 is associated with CANVAS but the contributions of RFC2-5 subunits on human Mendelian disorders is unknown.

Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6126 LARP1 Sangavi Sivagnanasundram gene: LARP1 was added
gene: LARP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: LARP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LARP1 were set to 39182167
Phenotypes for gene: LARP1 were set to Neurodevelopmental disorder; MONDO:0700092
Review for gene: LARP1 was set to GREEN
Added comment: Seven unrelated probands (6 males and 1 female) with ASD or another variable NDD phenotype (ID, hypotonia, motor delay and/or ASD). Variants were showed to be de novo null variants or missense variants that resulted in haploinsufficiency.

Ex vivo (knockout CRISPR-Cas9) functional assay using lymphoblasts that was collected and immortilised from one proband was conducted to assess the functional impact of the LARP1 variant. The results showed a reduction in protein compared to WT causing reduced rates of aerobic respiration and glycolysis
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6126 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6126 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6125 PNPLA8 Chirag Patel Classified gene: PNPLA8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6125 PNPLA8 Chirag Patel Gene: pnpla8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6124 PNPLA8 Chirag Patel gene: PNPLA8 was added
gene: PNPLA8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA8 were set to PMID: 39082157
Phenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases
Review for gene: PNPLA8 was set to GREEN
gene: PNPLA8 was marked as current diagnostic
Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 13/19 individuals (info available) had developmental delay and/or severe intellectual disability.

Using cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6123 MED22 Mark Cleghorn gene: MED22 was added
gene: MED22 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: MED22 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MED22 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: MED22 were set to unknown
Review for gene: MED22 was set to AMBER
Added comment: ESHG talk 2/6/24, unpublished
Elisa Cali, UCL

Recurrent homozygous MED22:c.397_399del (p.Glu133del) inframe variant in 8 individuals from 6 families w progressive NDD, microcepahly, cerebellar atrophy, dystonia, seizures

Rare in gnomad v4.1 (9 het alleles, no homozygotes)

Functional work on patient fibroblasts: quantity of protein comparable to controls, did not mentioned assays of protein function (?mechanism proposed)
Drosophilia heterozygous model with equivalent of p.Glu133del variant: structural anomalies, less movements, all died prior to pupae stage
Zebrafish: MED22 mutants less mobile, died prior to adulthood, reduced brain size
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 BICRA Mark Cleghorn reviewed gene: BICRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome-12, MIM#619325; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6123 SF3B1 Mark Cleghorn gene: SF3B1 was added
gene: SF3B1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: SF3B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SF3B1 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: SF3B1 were set to unknown
Review for gene: SF3B1 was set to AMBER
Added comment: SF3B1
Delphine Bernard, University of Brest
ESHG talk 2/6/24, unpublished

De novo germline SF3B1 variants, proposed spliceosomopathy/NDD gene

SF3B1 is an RNA binding protein that stabilizes the U2 snRNP complex at branchpoint sequences
Somatic SF3B1 missense commonly occur in haematological malignancy (K700E recurrent)

25 patients with syndromic NDD + de novo heterozygous rare SF3B1 variants identified on WES, genematcher
13 missense (incl recurrent xxx and xxx) within HEAT domain
5 nonsense
4 splicing
1 frameshift

Patients w missense variants may have more severe phenotype incl mircocepahly, palate anomalies, cerebral anomalies, GI/cardiac anomalies

Cellular models of missense variants: erythroluekaemia K562, HEK293T
Suggest missense variants do not cause loss of function, but increase exon skipping and alternative 3’ splice sites
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 C12orf66 Mark Cleghorn gene: C12orf66 was added
gene: C12orf66 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C12orf66 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: C12orf66 were set to unknown
Review for gene: C12orf66 was set to AMBER
Added comment: KICS2 (previously known as C12ORF66)
Rebecca Buchert, Universitatklinikum Tubingen
ESHG talk 2/6/24, unpublished

Proposed ID + epilepsy gene

8 families w 11 affected individuals
Phenotypes: 11/11 ID, 9/11 epilepsy, 3/11 hearing impairment
3/8 homozygous missense variants (p.Asp296Glu, p.Tyr393Cys, p.Tyr393Cys), all highly conserved
1/8 compound het PTC (p.Lys262*) with 1.1Mb deletion
4/8 homozygous PTC (p.Glu3*, p.Gly79Valfs*18, p.Gly79Valfs*18, p.Lys260Asnfs*18)

Gene appears to be involved in mTOR pathway, and cilia function
mTORC1 activity in CRISPR-HEK293T cells – reduced activity in cells w variants above

Zebrafish model: otolith defects, ciliary dysfunction
?not clear if truly mimics phenotype observed in patient cohort described
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 REPS2 Mark Cleghorn gene: REPS2 was added
gene: REPS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: REPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: REPS2 were set to complex neurodevelopmental disorder MONDO:0100038; Cerebral palsy HP:0100021
Penetrance for gene: REPS2 were set to unknown
Review for gene: REPS2 was set to AMBER
Added comment: REPS2
Hao Hu, Guangzhou Women and Children’s MC
ESHG talk 1/6/24, unpublished

Proposed X-linked cerebral palsy + NDD gene

4 unrelated males with predicted deleterious hemizygous REPS2 variants, 2 PTC, 2 missense. 2 de novo, 2 maternally inherited
Phenotypes: 2 w CP + moderate ID/ASD, 2 w NDD NOS
Variants described:
c.1050_1052delGAA;p.K351del
c.1040T>C; p.I347T
c.962C>G; p.S321C
c.1736delA; p.N579Tfs*17

In vitro assay of above 4 variants suggest reduced REPS2 protein stability
Zebrafish model: REPS2 expressed in neuronal cells, REPS2 knock down have reduced motor activity and abN neuronal morphology
Mouse model hemizygous w one of above variants (not specified): reduced performance in cognitive tasks, abnormal neuronal migration pattern on post mortem examination
Mechanism may relate to dopamine signalling?
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 TTL Mark Cleghorn gene: TTL was added
gene: TTL was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: TTL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTL were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: TTL was set to AMBER
Added comment: TTL
Valentina Serpieri, University of Pavia
ESHG talk 1/6/24

FAM1 (Italy)
2 affected sisters born to consanguineous Pakistani parents
GDD, spastic tetraparesis, optic atrophy, brain anomalies resembling tubulinopathies (dysplasia of corpus callosum, basal ganglia, brainstem)
WES: homozygous TTL:c.1013G>A; p.Cys338Tyr in both affected sisters

Via genematcher
5 more families (9 individuals) w similar phenotypes and biallelic variants in TTL

FAM2 (Egypt): homozygous p.Arg46Pro
FAM3 (Egypt): homozygous p.Arg46Pro
FAM4 (Australia): homozygous p.Gln183Arg
FAM5 (France): homozygous p.Trp147*
FAM6 (Saudi Arabia): homozygous p.His243Tyr

TTL KO mice: death soon after birth, no overt malformations, but defects in organisation of cerebral layers

Functional work on patient fibroblasts
FAM1 – reduced quantity of TTL protein compared to control on Western blot, decreased function of TTL protein (increase in detyrosinated tubulin) compared to controls – infer LoF as mechanism
FAM3 – mentioned but no details
FAM4– mentioned but no details
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6123 DHTKD1 Sumudu Perera reviewed gene: DHTKD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23141293, 37499576, 1112064, 6434826, 4442872, 4430147; Phenotypes: 2-aminoadipic 2-oxoadipic aciduria MIM#204750, Disorders of histidine, tryptophan or lysine metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6123 DCX Sumudu Perera edited their review of gene: DCX: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.6123 DARS2 Sumudu Perera reviewed gene: DARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17384640, 21815884, 20506600; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6123 DCX Sumudu Perera changed review comment from: Pathology:
PMID: 26743950 - DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females

Phenotype:
Demelas et al. (2001) (PMID:11468322) demonstrated three brothers with phenotype of microcephaly, mild to moderate developmental delay, seizures and other neurologic abnormalities, as well as classic lissencephaly on MRI.

Lawrence et al. (2010) (PMID: 20726879) discuss 3 male members had severe epilepsy and intellectual disability; finding of missense mutation in DCX. Of note all 3 had been diagnosed with Lennox-Gastaut syndrome.

GeneReviews (PMID: 20301364): "Males with classic DCX-related lissencephaly typically have early and profound cognitive and language impairment, cerebral palsy, and epileptic seizures. The clinical phenotype in females with SBH varies widely with cognitive abilities that range from average or mild cognitive impairment to severe intellectual disability and language impairment."

Other papers:
1) Somatic mosaicism and variable penetrance - PMID: 12552055
2) Functional testing: PMID: 9489699; to: Pathology:
PMID: 26743950 - DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females

Phenotype:
Demelas et al. (2001) (PMID:11468322) demonstrated three brothers with phenotype of microcephaly, mild to moderate developmental delay, seizures and other neurologic abnormalities, as well as classic lissencephaly on MRI.

Lawrence et al. (2010) (PMID: 20726879) discuss 3 male members had severe epilepsy and intellectual disability; finding of missense mutation in DCX. Of note all 3 had been diagnosed with Lennox-Gastaut syndrome.

GeneReviews (PMID: 20301364): "Males with classic DCX-related lissencephaly typically have early and profound cognitive and language impairment, cerebral palsy, and epileptic seizures. The clinical phenotype in females with SBH varies widely with cognitive abilities that range from average or mild cognitive impairment to severe intellectual disability and language impairment."

Other papers:
1) Somatic mosaicism and variable penetrance - PMID: 12552055
2) Functional testing: PMID: 9489699
Intellectual disability syndromic and non-syndromic v0.6123 DCX Sumudu Perera reviewed gene: DCX: Rating: ; Mode of pathogenicity: None; Publications: 26743950, 11468322, 20726879, 20301364, 12552055, 9489699; Phenotypes: Lissencephaly, X-linked, MIM# 300067, Subcortical laminal heterotopia, X-linked 300067; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6123 D2HGDH Sumudu Perera reviewed gene: D2HGDH: Rating: GREEN; Mode of pathogenicity: None; Publications: 15609246, 16081310, 31349060, 20020533, 38825343; Phenotypes: D-2-hydroxyglutaric aciduria MIM#600721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6123 GTPBP1 Zornitza Stark Phenotypes for gene: GTPBP1 were changed from Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related to Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888
Intellectual disability syndromic and non-syndromic v0.6122 GTPBP1 Zornitza Stark reviewed gene: GTPBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM# 620888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6122 CSNK1G1 Rylee Peters reviewed gene: CSNK1G1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33009664; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6122 CSMD1 Zornitza Stark Marked gene: CSMD1 as ready
Intellectual disability syndromic and non-syndromic v0.6122 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6122 CSMD1 Zornitza Stark Classified gene: CSMD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6122 CSMD1 Zornitza Stark Gene: csmd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6121 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autisim and ID GCEP.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6120 ZSCAN10 Zornitza Stark reviewed gene: ZSCAN10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Otofacial neurodevelopmental syndrome, MIM# 620910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6120 COQ8A Zornitza Stark Marked gene: COQ8A as ready
Intellectual disability syndromic and non-syndromic v0.6120 COQ8A Zornitza Stark Gene: coq8a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6120 COQ8A Zornitza Stark Phenotypes for gene: COQ8A were changed from to coenzyme Q10 deficiency MONDO:0018151
Intellectual disability syndromic and non-syndromic v0.6119 COQ8A Zornitza Stark Publications for gene: COQ8A were set to
Intellectual disability syndromic and non-syndromic v0.6118 COQ8A Zornitza Stark Mode of inheritance for gene: COQ8A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6117 CTDP1 Zornitza Stark Marked gene: CTDP1 as ready
Intellectual disability syndromic and non-syndromic v0.6117 CTDP1 Zornitza Stark Gene: ctdp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6117 CTDP1 Zornitza Stark Phenotypes for gene: CTDP1 were changed from to congenital cataracts-facial dysmorphism-neuropathy syndrome MONDO:0011402
Intellectual disability syndromic and non-syndromic v0.6116 CTDP1 Zornitza Stark Publications for gene: CTDP1 were set to
Intellectual disability syndromic and non-syndromic v0.6115 CTDP1 Zornitza Stark Mode of inheritance for gene: CTDP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6114 CTSA Zornitza Stark Marked gene: CTSA as ready
Intellectual disability syndromic and non-syndromic v0.6114 CTSA Zornitza Stark Gene: ctsa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6114 CTSA Zornitza Stark Phenotypes for gene: CTSA were changed from to Galactosialidosis MONDO:0009737
Intellectual disability syndromic and non-syndromic v0.6113 CTSA Zornitza Stark Publications for gene: CTSA were set to
Intellectual disability syndromic and non-syndromic v0.6112 CTSA Zornitza Stark Mode of inheritance for gene: CTSA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6111 CTSD Zornitza Stark Marked gene: CTSD as ready
Intellectual disability syndromic and non-syndromic v0.6111 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6111 CTSD Zornitza Stark Phenotypes for gene: CTSD were changed from to neuronal ceroid lipofuscinosis MONDO:0016295
Intellectual disability syndromic and non-syndromic v0.6110 CTSD Zornitza Stark Mode of inheritance for gene: CTSD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6109 CYB5R3 Zornitza Stark Marked gene: CYB5R3 as ready
Intellectual disability syndromic and non-syndromic v0.6109 CYB5R3 Zornitza Stark Gene: cyb5r3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6109 CYB5R3 Zornitza Stark Phenotypes for gene: CYB5R3 were changed from to Methemoglobinemia MONDO:0001117
Intellectual disability syndromic and non-syndromic v0.6108 CYB5R3 Zornitza Stark Publications for gene: CYB5R3 were set to
Intellectual disability syndromic and non-syndromic v0.6107 CYB5R3 Zornitza Stark Mode of inheritance for gene: CYB5R3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6106 SOX9 Zornitza Stark Marked gene: SOX9 as ready
Intellectual disability syndromic and non-syndromic v0.6106 SOX9 Zornitza Stark Gene: sox9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6106 SOX9 Zornitza Stark Phenotypes for gene: SOX9 were changed from to campomelic dysplasia MONDO:0007251
Intellectual disability syndromic and non-syndromic v0.6105 SOX9 Zornitza Stark Publications for gene: SOX9 were set to
Intellectual disability syndromic and non-syndromic v0.6104 SOX9 Zornitza Stark Mode of inheritance for gene: SOX9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6103 SOX9 Zornitza Stark Classified gene: SOX9 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6103 SOX9 Zornitza Stark Gene: sox9 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6102 SOX9 Zornitza Stark changed review comment from: Agree ID typically not part of the phenotype. Note reports of milder cases and DD/ID reported in some survivors, therefore downgraded to Amber.; to: Agree ID typically not part of the phenotype. Note reports of milder cases and DD/ID reported in some survivors (this publication suggests >80%), therefore downgraded to Amber.
Intellectual disability syndromic and non-syndromic v0.6102 SOX9 Zornitza Stark reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: None; Publications: 21373255; Phenotypes: campomelic dysplasia MONDO:0007251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6102 SOX9 Zornitza Stark Classified gene: SOX9 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.6102 SOX9 Zornitza Stark Gene: sox9 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6101 GLS Zornitza Stark Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412 to Epileptic encephalopathy, early infantile, 71, MIM# 618328; Global developmental delay, progressive ataxia, and elevated glutamine, MIM# 618412
Intellectual disability syndromic and non-syndromic v0.6100 GLS Zornitza Stark Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6099 HDAC3 Zornitza Stark Marked gene: HDAC3 as ready
Intellectual disability syndromic and non-syndromic v0.6099 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6099 SOX9 Ken Lee Wan reviewed gene: SOX9: Rating: RED; Mode of pathogenicity: None; Publications: 20301724, 26663529; Phenotypes: campomelic dysplasia MONDO:0007251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6099 TBC1D7 Zornitza Stark Publications for gene: TBC1D7 were set to 24515783; 23687350
Intellectual disability syndromic and non-syndromic v0.6098 TBC1D7 Zornitza Stark Classified gene: TBC1D7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6098 TBC1D7 Zornitza Stark Gene: tbc1d7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6097 TBC1D7 Zornitza Stark edited their review of gene: TBC1D7: Added comment: PMID: 36669495 reports additional individuals with compound het variants identified via trio RNASeq.; Changed rating: GREEN; Changed publications: 24515783, 23687350, 36669495
Intellectual disability syndromic and non-syndromic v0.6097 MSL2 Zornitza Stark Classified gene: MSL2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6097 MSL2 Zornitza Stark Gene: msl2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6096 CYB5R3 Ken Lee Wan reviewed gene: CYB5R3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38303731; Phenotypes: Methemoglobinemia MONDO:0001117; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6096 CTSD Ken Lee Wan reviewed gene: CTSD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neuronal ceroid lipofuscinosis MONDO:0016295; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6096 CTSA Ken Lee Wan reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23915561, 36713078; Phenotypes: Galactosialidosis MONDO:0009737; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6096 CTDP1 Ken Lee Wan reviewed gene: CTDP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301787; Phenotypes: congenital cataracts-facial dysmorphism-neuropathy syndrome MONDO:0011402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6096 HDAC3 Zornitza Stark edited their review of gene: HDAC3: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Intellectual disability syndromic and non-syndromic v0.6096 HDAC3 Zornitza Stark Phenotypes for gene: HDAC3 were changed from to Neurodevelopmental disorder, MONDO:0700092, HDAC3-related
Intellectual disability syndromic and non-syndromic v0.6095 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6095 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6094 HDAC3 Zornitza Stark Classified gene: HDAC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6094 HDAC3 Zornitza Stark Gene: hdac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6093 HDAC3 Zornitza Stark gene: HDAC3 was added
gene: HDAC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HDAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC3 were set to 39047730
Review for gene: HDAC3 was set to GREEN
Added comment: Six individuals with de novo missense variants in this gene and variable NDD phenotypes, including ID, seizures. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Marked gene: SLC39A14 as ready
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Gene: slc39a14 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6092 SLC39A14 Zornitza Stark Mode of inheritance for gene: SLC39A14 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6091 SLC39A14 Zornitza Stark Publications for gene: SLC39A14 were set to
Intellectual disability syndromic and non-syndromic v0.6090 SLC39A14 Zornitza Stark Phenotypes for gene: SLC39A14 were changed from to Hypermanganesemia with dystonia 2 (MIM# 617013)
Intellectual disability syndromic and non-syndromic v0.6089 COQ8A Ken Lee Wan reviewed gene: COQ8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31621627, 31741144; Phenotypes: coenzyme Q10 deficiency MONDO:0018151; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Marked gene: COL4A2 as ready
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Gene: col4a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6089 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496 to Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496
Intellectual disability syndromic and non-syndromic v0.6088 COL4A2 Zornitza Stark Phenotypes for gene: COL4A2 were changed from to Brain small vessel disease 2, MIM# 614483; familial porencephaly MONDO:0020496
Intellectual disability syndromic and non-syndromic v0.6087 COL4A2 Zornitza Stark Publications for gene: COL4A2 were set to
Intellectual disability syndromic and non-syndromic v0.6086 COL4A2 Zornitza Stark Mode of inheritance for gene: COL4A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Marked gene: COQ4 as ready
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6085 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562
Intellectual disability syndromic and non-syndromic v0.6084 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from Coenzyme Q10 deficiency, primary, 7, MIM# 616276 to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562
Intellectual disability syndromic and non-syndromic v0.6084 COQ4 Zornitza Stark Phenotypes for gene: COQ4 were changed from to Coenzyme Q10 deficiency, primary, 7, MIM# 616276
Intellectual disability syndromic and non-syndromic v0.6083 COQ4 Zornitza Stark Publications for gene: COQ4 were set to 34656997
Intellectual disability syndromic and non-syndromic v0.6083 COQ4 Zornitza Stark Publications for gene: COQ4 were set to
Intellectual disability syndromic and non-syndromic v0.6082 COQ4 Zornitza Stark Mode of inheritance for gene: COQ4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6081 COQ4 Ken Lee Wan reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34656997; Phenotypes: mitochondrial disease MONDO:0044970, neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome MONDO:0014562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6081 COL4A2 Ken Lee Wan reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36324412, 39016117; Phenotypes: familial porencephaly MONDO:0020496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Marked gene: CLN8 as ready
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Gene: cln8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6081 CLN8 Zornitza Stark Phenotypes for gene: CLN8 were changed from to neuronal ceroid lipofuscinosis MONDO:0016295
Intellectual disability syndromic and non-syndromic v0.6080 CLN8 Zornitza Stark Mode of inheritance for gene: CLN8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6079 CLN8 Ken Lee Wan reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neuronal ceroid lipofuscinosis MONDO:0016295; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Marked gene: LEO1 as ready
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Gene: leo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Classified gene: LEO1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6079 LEO1 Zornitza Stark Gene: leo1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6078 LEO1 Zornitza Stark gene: LEO1 was added
gene: LEO1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LEO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LEO1 were set to 38965372
Phenotypes for gene: LEO1 were set to neurodevelopmental disorder MONDO:0700092, LEO-1 related
Review for gene: LEO1 was set to AMBER
Added comment: cohort of individuals with delayed motor and speech development, ASD

8x de novo – 6x missense + 2x PTC
1x pat splice (father unaffected)
2x unknown_inh PTCs

Of the missense variants, G370E has 8 hets in gnomad v4

This gene is not constraint for LoF with 4 hets with an NMD variant in gnomad v4
3 of the missense are said to lie within a region of missense constraint, however this isn't the case in v4
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6077 CHD2 Zornitza Stark Phenotypes for gene: CHD2 were changed from Epileptic encephalopathy, childhood-onset (MIM # 615369) to Developmental and epileptic encephalopathy 94, MIM# 615369
Intellectual disability syndromic and non-syndromic v0.6076 CHD2 Zornitza Stark Publications for gene: CHD2 were set to
Intellectual disability syndromic and non-syndromic v0.6075 CHD2 Zornitza Stark reviewed gene: CHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 94, MIM# 615369; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6075 CHD2 Ken Lee Wan reviewed gene: CHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26677509; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6075 RBBP5 Ain Roesley Phenotypes for gene: RBBP5 were changed from to neurodevelopmental disorder MONDO:0700092, RBBP5-related
Intellectual disability syndromic and non-syndromic v0.6074 RBBP5 Ain Roesley edited their review of gene: RBBP5: Changed phenotypes: neurodevelopmental disorder MONDO:0700092, RBBP5-related
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Marked gene: PCBP2 as ready
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Classified gene: PCBP2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6074 PCBP2 Ain Roesley Gene: pcbp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6073 PCBP2 Ain Roesley gene: PCBP2 was added
gene: PCBP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PCBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PCBP2 were set to 38965372
Phenotypes for gene: PCBP2 were set to neurodevelopmental disorder MONDO:0700092, PCBP2-related
Review for gene: PCBP2 was set to GREEN
gene: PCBP2 was marked as current diagnostic
Added comment: 3x individuals with de novo variants
Motor and speech delay and ASD
2x missense + 1x fs

There are 2 NMD variants with 9 and 8 hets respectively in gnomad v4, however the IGV looks to be low quality
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6072 SLC45A1 Zornitza Stark Publications for gene: SLC45A1 were set to 28434495
Intellectual disability syndromic and non-syndromic v0.6071 SLC45A1 Zornitza Stark Classified gene: SLC45A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6071 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6070 SLC45A1 Zornitza Stark edited their review of gene: SLC45A1: Added comment: PMID 39003656: additional individual with compound het missense variants and supportive functional data.; Changed rating: GREEN; Changed publications: 28434495, 39003656
Intellectual disability syndromic and non-syndromic v0.6070 SRPK3 Zornitza Stark Publications for gene: SRPK3 were set to 38429495; 39073169
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark edited their review of gene: SRPK3: Changed publications: 39073169
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Marked gene: SRPK3 as ready
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Classified gene: SRPK3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6069 SRPK3 Zornitza Stark Gene: srpk3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6068 SRPK3 Zornitza Stark gene: SRPK3 was added
gene: SRPK3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SRPK3 were set to 38429495; 39073169
Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related
Review for gene: SRPK3 was set to GREEN
Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Marked gene: RBBP5 as ready
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Classified gene: RBBP5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Classified gene: RBBP5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6067 RBBP5 Ain Roesley Gene: rbbp5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6066 RBBP5 Ain Roesley gene: RBBP5 was added
gene: RBBP5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RBBP5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBBP5 were set to 39036895
Review for gene: RBBP5 was set to GREEN
gene: RBBP5 was marked as current diagnostic
Added comment: 5x Indivs (4x de novo) = 3x PTCs + 2x missense

4/5 dev delay/ID
2/5 short stature (<=-3 SD) + 2/5 <= -2 SD
1/5 microcephaly (<= -3 SD) + 3/5 <= -2 SD
2/5 SNHL
2/5 seizures
3/5 hypotonia
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Marked gene: NDC1 as ready
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Classified gene: NDC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6065 NDC1 Bryony Thompson Gene: ndc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6064 NDC1 Bryony Thompson gene: NDC1 was added
gene: NDC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NDC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDC1 were set to 39003500; 19782045
Phenotypes for gene: NDC1 were set to triple-A syndrome MONDO:0009279
Review for gene: NDC1 was set to GREEN
Added comment: 7 cases from 4 consanguineous families (3 different variants: 1 intronic variants that causes in-frame RNA splice impact, 2 missense) with a Triple-A-like syndrome (including ID and neuropathy). Supporting cellular localisation studies were conducted in patient cell lines with the splice variant. NDC1 is required to anchor ALADIN (encoded by AAAS, the gene that causes Triple-A syndrome) in the nuclear pore complex.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6063 SLC39A14 Kushani Jayasinghe reviewed gene: SLC39A14: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27231142, 29685658; Phenotypes: Hypermanganesemia with dystonia 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Marked gene: SPATA5 as ready
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is AFG2A
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 SPATA5 Zornitza Stark Tag new gene name tag was added to gene: SPATA5.
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Marked gene: CRNKL1 as ready
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Classified gene: CRNKL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6063 CRNKL1 Zornitza Stark Gene: crnkl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6062 CRNKL1 Mark Cleghorn gene: CRNKL1 was added
gene: CRNKL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: CRNKL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CRNKL1 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: CRNKL1 were set to Complete
Review for gene: CRNKL1 was set to GREEN
Added comment: Unpublished, presented at ESHG June 2024 - Louise Bicknell, University of Otago NZ
8 unrelated families via gene matcher with rare, de novo, missense variants in CRNKL1
severe microcephaly (all, -8 to -11 SD)
ID/epilepsy
pontocerebellar hypoplasia (6/8)
simplified gyration (8/8)
7 variants are missense at p.Arg267 residue
1 variant missense at p.Arg301
RNA-seq on patient fibroblasts - no alteration in gene expression
Zebrafish homolog of Arg267 and Arg301 - mimics observed phenotype (reduced brain development), increased in embryo apoptosis
RNQ seq on affected zebrafish embryos - transcriptome strongly disrupted
Splicing analysis in progress

CRKNL1 supports U6 structure in spliceosome
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6062 B9D1 Achchuthan Shanmugasundram reviewed gene: B9D1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 32622957; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6062 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to 38645094
Intellectual disability syndromic and non-syndromic v0.6061 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38991538
Intellectual disability syndromic and non-syndromic v0.6061 FDXR Zornitza Stark Publications for gene: FDXR were set to 30250212
Intellectual disability syndromic and non-syndromic v0.6060 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717 to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6059 FDXR Zornitza Stark Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM# 617717 to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887; Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6058 FDXR Zornitza Stark Classified gene: FDXR as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6058 FDXR Zornitza Stark Gene: fdxr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6057 FDXR Zornitza Stark edited their review of gene: FDXR: Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression.; Changed rating: GREEN; Changed publications: 30250212, 29040572, 33348459, 37046037, 37481223; Changed phenotypes: Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887, Auditory neuropathy and optic atrophy, MIM# 617717
Intellectual disability syndromic and non-syndromic v0.6057 RNU4-2 Zornitza Stark Phenotypes for gene: RNU4-2 were changed from Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related to Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Intellectual disability syndromic and non-syndromic v0.6056 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed phenotypes: Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language, MIM# 620851
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6056 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6055 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF2 were set to 38847193
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related
Review for gene: SREBF2 was set to AMBER
Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6054 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Developmental disorders to Neurodevelopmental disorder (MONDO#0700092), PSMC5-related
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Classified gene: PSMC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Marked gene: PSMF1 as ready
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Classified gene: PSMF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6052 PSMF1 Zornitza Stark Gene: psmf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6051 PSMF1 Zornitza Stark gene: PSMF1 was added
gene: PSMF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to https://www.medrxiv.org/content/10.1101/2024.06.19.24308302v1
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Review for gene: PSMF1 was set to GREEN
Added comment: 22 individuals from 15 families reported with a range of neurological phenotypes ranging from early-onset Parkinson's disease; childhood conditions typified by ID and a range of movement disorders; through to perinatal lethal presentations with arthrogryposis multiplex. Genotype-phenotype correlation: biallelic missense variants resulted in the milder phenotypes, while bi-allelic LoF variants in the more severe phenotypes. Supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6050 PSMC5 Rylee Peters reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38776958, 38293138; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PSMC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Classified gene: VPS50 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Gene: vps50 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6050 VPS50 Ain Roesley Publications for gene: VPS50 were set to 34037727
Intellectual disability syndromic and non-syndromic v0.6049 VPS50 Ain Roesley reviewed gene: VPS50: Rating: GREEN; Mode of pathogenicity: None; Publications: 38876772; Phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis MIM#619685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Marked gene: PSMD11 as ready
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Classified gene: PSMD11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6049 PSMD11 Bryony Thompson Gene: psmd11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6048 PSMD11 Bryony Thompson gene: PSMD11 was added
gene: PSMD11 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMD11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMD11 were set to 38866022; 30733659
Phenotypes for gene: PSMD11 were set to Neurodevelopmental disorder, MONDO:0700092, PSMD11-related
Review for gene: PSMD11 was set to GREEN
Added comment: PMID: 38866022 - 10 unrelated children with early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity. Cognitive impairment is recapitulated in a drosophila model. Loss of function is the mechanism of disease

PMID: 30733659 - 4 probands with ID and different 17q11.2 deletions spanning PSMD11
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Marked gene: PAK2 as ready
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Classified gene: PAK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6047 PAK2 Ain Roesley Gene: pak2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6046 PAK2 Ain Roesley gene: PAK2 was added
gene: PAK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784; 38894571; 38712026
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome MIM#618458
Review for gene: PAK2 was set to GREEN
gene: PAK2 was marked as current diagnostic
Added comment: total of 3 families including 2 siblings with intra-familial variability

Siblings' phenotypes:
Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy.

Other 2 pro bands:
GDD, delayed motor (but normal verbal) skills, hypotonia

Missense variants with in vitro functional demonstrating reduction in PAK2 auto phosphorylation
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6045 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086 to Intellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Intellectual disability syndromic and non-syndromic v0.6044 MTSS1L Ain Roesley Phenotypes for gene: MTSS1L were changed from Intellectual disability, MTSS2-related (MONDO#0001071) to ntellectual developmental disorder with ocular anomalies and distinctive facial features MIM#620086
Intellectual disability syndromic and non-syndromic v0.6043 ZNF292 Ain Roesley Phenotypes for gene: ZNF292 were changed from Intellectual developmental disorder, autosomal dominant 63, MIM# 619188; Intellectual disability; autism; ADHD to Intellectual developmental disorder, autosomal dominant 64 MIM#619188
Intellectual disability syndromic and non-syndromic v0.6042 MYH10 Zornitza Stark Phenotypes for gene: MYH10 were changed from Microcephaly; Intellectual Disability to AD complex neurodevelopmental disorder with or without congenital anomalies (MONDO:0100465)
Intellectual disability syndromic and non-syndromic v0.6041 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type 309548 to Intellectual disability, X-linked, FRAXE type 309548
Intellectual disability syndromic and non-syndromic v0.6040 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 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 syndromic and non-syndromic v0.6039 AFF2 Zornitza Stark Mode of inheritance for gene: AFF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6038 AFF2 Zornitza Stark edited their review of gene: AFF2: Changed phenotypes: Intellectual disability, X-linked, FRAXE type 309548; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark Marked gene: RDH14 as ready
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark Gene: rdh14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6038 RDH14 Zornitza Stark gene: RDH14 was added
gene: RDH14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RDH14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RDH14 were set to 34848785
Phenotypes for gene: RDH14 were set to Neurodevelopmental disorder, MONDO:0700092, RDH14-related
Review for gene: RDH14 was set to RED
Added comment: Two related individuals with ID and cerebellar atrophy and homozygous LoF variant reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Marked gene: ATXN7L3 as ready
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Gene: atxn7l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6037 ATXN7L3 Zornitza Stark Phenotypes for gene: ATXN7L3 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, ATXN7L3-related
Intellectual disability syndromic and non-syndromic v0.6036 PTEN Ain Roesley Phenotypes for gene: PTEN were changed from Cowden syndrome 1 MIM#158350; Macrocephaly/autism syndrome MIM#605309 to Cowden syndrome 1 MIM#158350; Macrocephaly/autism syndrome MIM#605309; PTEN hamartoma tumor syndrome MONDO:0017623
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Marked gene: FAM177A1 as ready
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6035 FAM177A1 Zornitza Stark Phenotypes for gene: FAM177A1 were changed from Neurodevelopmental disorder, MONDO_0100500 to Neurodevelopmental disorder, MONDO_0100500, FAM177a1-related
Intellectual disability syndromic and non-syndromic v0.6034 SLC6A1 Zornitza Stark Publications for gene: SLC6A1 were set to 29315614
Intellectual disability syndromic and non-syndromic v0.6033 SLC6A1 Zornitza Stark edited their review of gene: SLC6A1: Added comment: Haploinsufficiency established as the mechanism.; Changed publications: 29315614, 38781976
Intellectual disability syndromic and non-syndromic v0.6033 MSL2 Zornitza Stark Phenotypes for gene: MSL2 were changed from Developmental disorders; autism to Neurodevelopmental disorder, MONDO:0700092, MSL2-related
Intellectual disability syndromic and non-syndromic v0.6032 MSL2 Sangavi Sivagnanasundram reviewed gene: MSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38815585, 38702431; Phenotypes: MSL2-Related Developmental Disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6032 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6032 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Marked gene: ANO4 as ready
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Classified gene: ANO4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6031 ANO4 Ain Roesley Gene: ano4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6030 ANO4 Ain Roesley gene: ANO4 was added
gene: ANO4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ANO4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANO4 were set to 38744284
Phenotypes for gene: ANO4 were set to neurodevelopmental disorder MONDO:0700092, ANO4-related
Review for gene: ANO4 was set to GREEN
gene: ANO4 was marked as current diagnostic
Added comment: aka TMEM16D

5x de novo + 2x inherited missense (73% penetrance + asymptomatic)

the ones with de novo variants:
all had ID, hypotonia
4x skeletal features (scoliosis, funnel chest, pet plants, hyper extensible joints)

all had epilepsy
all had abnormal MRI
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6029 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6029 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Marked gene: KCND1 as ready
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Classified gene: KCND1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6028 KCND1 Ain Roesley Gene: kcnd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6027 KCND1 Ain Roesley gene: KCND1 was added
gene: KCND1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KCND1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KCND1 were set to 38772379
Phenotypes for gene: KCND1 were set to neurodevelopmental disorder MONDO:0700092, KCND1-related
Review for gene: KCND1 was set to GREEN
gene: KCND1 was marked as current diagnostic
Added comment: 18 males from 17 families
2x de novo missense + 3x maternal NMDs + 12x maternal missense
Some functional studies were done

14x ID
4x delayed motor dev
7x muscular hypotonia
6x epilepsy
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6026 ATXN7L3 Chirag Patel Classified gene: ATXN7L3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6026 ATXN7L3 Chirag Patel Gene: atxn7l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6025 ATXN7L3 Chirag Patel gene: ATXN7L3 was added
gene: ATXN7L3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATXN7L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATXN7L3 were set to PMID: 38753057
Phenotypes for gene: ATXN7L3 were set to Neurodevelopmental disorder, MONDO_0100500
Review for gene: ATXN7L3 was set to GREEN
gene: ATXN7L3 was marked as current diagnostic
Added comment: This study reports 9 unrelated individuals with de novo heterozygous variants in ATXN7L3 identified through WES testing and GeneMatcher. Core clinical features included: global motor and language developmental delay, hypotonia, and dysmorphic features (hypertelorism, epicanthal folds, blepharoptosis, small nose, small mouth, and low-set posteriorly rotated ears). Variable features included: feeding difficulties, seizures, mild periventricular leukomalacia, and structural cardiac abnormalities.

A recurrent nonsense variant [p.(Arg114Ter)] was found in 5/9 individuals. The other variants were 1 frameshift [p.(Ser112LysfsTer12)] and 3 missense variants [p.(Ile71Thr), p.(Ser92Arg), and p.(Leu106Pro)]. They investigated the effects of the recurrent nonsense variant [p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired (as indicated by an increase in histone H2Bub1 levels). This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality.

Pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders (ND) and congenital abnormalities. ATXN7L3 is a component of the DUB module of the SAGA complex, and two other related DUB modules, and serves as an obligate adaptor protein of 3 ubiquitin-specific proteases (USP22, USP27X or USP51).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6024 FAM177A1 Chirag Patel Classified gene: FAM177A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6024 FAM177A1 Chirag Patel Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6023 FAM177A1 Chirag Patel Classified gene: FAM177A1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6023 FAM177A1 Chirag Patel Gene: fam177a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6022 FAM177A1 Chirag Patel gene: FAM177A1 was added
gene: FAM177A1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FAM177A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM177A1 were set to PMID: 38767059, 25558065
Phenotypes for gene: FAM177A1 were set to Neurodevelopmental disorder, MONDO_0100500
Review for gene: FAM177A1 was set to GREEN
gene: FAM177A1 was marked as current diagnostic
Added comment: PMID: 38767059
5 individuals from 3 unrelated families reported with with biallelic loss of function variants in FAM177A1. Clinical features included: global developmental delay, intellectual disability, seizures, behavioural abnormalities, hypotonia, gait disturbance, and macrocephaly.

They showed that FAM177A1 localizes to the Golgi complex in mammalian and zebrafish cells. Intersection of the RNA-seq and metabolomic datasets from FAM177A1-deficient human fibroblasts and whole zebrafish larvae demonstrated dysregulation of pathways associated with apoptosis, inflammation, and negative regulation of cell proliferation.

PMID: 25558065
A study of 143 multiplex consanguineous families identified a homozygous frameshift variant in FAM177A1 in 1 family with 4 affected siblings with intellectual disability, dolicocephaly, obesity, and macrocephaly. The variant segregated with all 4 affected siblings and parents were confirmed heterozygous carriers.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6021 ERF Chirag Patel Classified gene: ERF as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6021 ERF Chirag Patel Gene: erf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6020 ERF Chirag Patel reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38824261; Phenotypes: Noonan syndrome-like with or without craniosynostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6020 PPFIA3 Zornitza Stark Publications for gene: PPFIA3 were set to 37034625
Intellectual disability syndromic and non-syndromic v0.6019 PPFIA3 Zornitza Stark edited their review of gene: PPFIA3: Changed publications: 38723631
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Marked gene: SSR4 as ready
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Gene: ssr4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6019 SSR4 Zornitza Stark Phenotypes for gene: SSR4 were changed from to Congenital disorder of glycosylation, type Iy, MIM# 300934
Intellectual disability syndromic and non-syndromic v0.6018 SSR4 Zornitza Stark Publications for gene: SSR4 were set to
Intellectual disability syndromic and non-syndromic v0.6017 SSR4 Zornitza Stark Mode of inheritance for gene: SSR4 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6016 SSR4 Zornitza Stark reviewed gene: SSR4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type Iy, MIM# 300934; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Marked gene: RELN as ready
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Gene: reln has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6016 RELN Zornitza Stark Publications for gene: RELN were set to
Intellectual disability syndromic and non-syndromic v0.6015 RELN Zornitza Stark reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 2 (Norman-Roberts type), MIM# 257320; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6015 RELN Zornitza Stark Phenotypes for gene: RELN were changed from to Lissencephaly 2 (Norman-Roberts type), MIM# 257320
Intellectual disability syndromic and non-syndromic v0.6014 RELN Zornitza Stark Mode of inheritance for gene: RELN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6013 SLC35A1 Anissa Johnson Deleted their review
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller changed review comment from: 7 individuals from 4 families with biallelic variants, and 13 individuals from 7 families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Associated features: intellectual disability (16/20), seizures (5/20), unprovoked aggression (6/20), sleep disturbance (7/20)
Variant spectrum includes: loss of function, missense, splice-site variants.

MRI features include: anterior-predominant “thin”lisencephaly pachygyria with cerebellar hypoplasia
Biallelic variants are associated with a severe phenotype that includes cerebellar hypoplasia.
Monoallelic variants are associated with incomplete penetrance and variable expressivity (eg: one adult with abnormal MRI but normal intelligence and neurological profile).; to: 7 individuals from 4 families with biallelic variants, and 13 individuals from 7 families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Associated features: intellectual disability (16/20), seizures (5/20), unprovoked aggression (6/20), sleep disturbance (7/20)
Variant spectrum includes: loss of function, missense, splice-site variants.

MRI features include: anterior-predominant “thin” lisencephaly pachygyria with cerebellar hypoplasia.
Biallelic variants are associated with a severe phenotype that includes cerebellar hypoplasia.
Monoallelic variants are associated with incomplete penetrance and variable expressivity (eg: one adult with abnormal MRI but normal intelligence and neurological profile).
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller edited their review of gene: RELN: Changed publications: PMID: 35769015, PMID: 29671837
Intellectual disability syndromic and non-syndromic v0.6013 RELN Tashunka Taylor-Miller reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35769015, 29671837; Phenotypes: OMIM *600514, HP:0001339, DOID:0070338; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Marked gene: DPYD as ready
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Gene: dpyd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6013 DPYD Zornitza Stark Phenotypes for gene: DPYD were changed from to Dihydropyrimidine dehydrogenase deficiency (MIM#274270)
Intellectual disability syndromic and non-syndromic v0.6012 DPYD Zornitza Stark Publications for gene: DPYD were set to
Intellectual disability syndromic and non-syndromic v0.6011 DPYD Zornitza Stark Mode of inheritance for gene: DPYD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6010 DPYD Zornitza Stark Classified gene: DPYD as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6010 DPYD Zornitza Stark Gene: dpyd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Marked gene: DMD as ready
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6009 DMD Zornitza Stark Phenotypes for gene: DMD were changed from to Duchenne muscular dystrophy MIM#310200
Intellectual disability syndromic and non-syndromic v0.6008 DMD Zornitza Stark Mode of inheritance for gene: DMD was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6007 DMD Zornitza Stark Tag SV/CNV tag was added to gene: DMD.
Intellectual disability syndromic and non-syndromic v0.6007 DMD Zornitza Stark reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Duchenne muscular dystrophy MIM#310200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6007 SSR4 Katie Thompson changed review comment from: Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein; to: Decipher - disorder of glycosolation (XLR), strong evidence
ORPHA:370927 GenCC strong. Not in gene2phenotype.
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein. All variants caused loss of function mainly from premature termination.
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Marked gene: COG7 as ready
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Gene: cog7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6007 COG7 Zornitza Stark Phenotypes for gene: COG7 were changed from to Congenital disorder of glycosylation, type IIe , MIM#608779
Intellectual disability syndromic and non-syndromic v0.6006 COG7 Zornitza Stark Publications for gene: COG7 were set to
Intellectual disability syndromic and non-syndromic v0.6005 COG7 Zornitza Stark Mode of inheritance for gene: COG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6005 COG7 Zornitza Stark Mode of inheritance for gene: COG7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6004 COG7 Zornitza Stark reviewed gene: COG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 15107842, 17356545, 28883096; Phenotypes: Congenital disorder of glycosylation, type IIe , MIM#608779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6004 SSR4 Katie Thompson changed review comment from: PMID: 24218363; 26264460
SSR4
Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females; to: Decipher - only disorder of glycosolation (XLR)
ORPHA:370927
OMIM: 300934. 2 good quality papers, one with 4 unrelated families, two with mendelian inheritance. Evidence of less severe phenotype in heterozygote females
Western blot showed complete loss of protein
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Marked gene: COG1 as ready
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Gene: cog1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6004 COG1 Zornitza Stark Phenotypes for gene: COG1 were changed from to Congenital disorder of glycosylation, type IIg, MIM# 611209
Intellectual disability syndromic and non-syndromic v0.6003 COG1 Zornitza Stark Publications for gene: COG1 were set to
Intellectual disability syndromic and non-syndromic v0.6002 COG1 Zornitza Stark Mode of inheritance for gene: COG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6001 SSR4 Katie Thompson reviewed gene: SSR4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24218363, 26264460; Phenotypes: intellectual disabilities, hypotonia, microcephaly, seizures, Feeding problems, Facial dysmorphism, Gastrointestinal abnormalities, Failure to thrive, strabismus; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6001 COG1 Zornitza Stark reviewed gene: COG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16537452, 19008299, 17904886, 11980916; Phenotypes: Congenital disorder of glycosylation, type IIg, MIM# 611209; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6001 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from to COL4A1-related disorder MONDO:0800461
Intellectual disability syndromic and non-syndromic v0.6000 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to
Intellectual disability syndromic and non-syndromic v0.5999 COL4A1 Zornitza Stark Mode of inheritance for gene: COL4A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Marked gene: SNAP29 as ready
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5998 SNAP29 Zornitza Stark Phenotypes for gene: SNAP29 were changed from to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (MIM#609528)
Intellectual disability syndromic and non-syndromic v0.5997 SNAP29 Zornitza Stark Publications for gene: SNAP29 were set to
Intellectual disability syndromic and non-syndromic v0.5997 SNAP29 Zornitza Stark Mode of inheritance for gene: SNAP29 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5996 SNAP29 Zornitza Stark Mode of inheritance for gene: SNAP29 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5995 SNAP29 Zornitza Stark reviewed gene: SNAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (MIM#609528); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5995 GABRA4 Zornitza Stark Marked gene: GABRA4 as ready
Intellectual disability syndromic and non-syndromic v0.5995 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5995 GABRA4 Zornitza Stark Phenotypes for gene: GABRA4 were changed from Developmental delay; Intellectual disability; Epileptic seizures to Neurodevelopmental disorder MONDO:0700092, GABRA4-related
Intellectual disability syndromic and non-syndromic v0.5994 GABRA4 Zornitza Stark Classified gene: GABRA4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5994 GABRA4 Zornitza Stark Gene: gabra4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5993 GABRA4 Zornitza Stark reviewed gene: GABRA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder MONDO:0700092, GABRA4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5993 SNAP29 Gunjan Garg reviewed gene: SNAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33977139, 30793783, 29051910; Phenotypes: cerebral dysgenesis, 609528, Global developmental delay, schizencephaly, polymicrogyria, intellectual disability, neurodevelopment delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5993 COL4A1 Hali Van Niel reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30413629, 33912663, 36786861, 32042920; Phenotypes: COL4A1-related disorder MONDO:0800461, brain small vessel disease 1 with or without ocular anomalies MONDO:0008289, microangiopathy and leukoencephalopathy, pontine, autosomal dominant MONDO:0032814; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5993 CLN6 Zornitza Stark Marked gene: CLN6 as ready
Intellectual disability syndromic and non-syndromic v0.5993 CLN6 Zornitza Stark Gene: cln6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5993 CLN6 Zornitza Stark Phenotypes for gene: CLN6 were changed from to Ceroid lipofuscinosis, neuronal, 6, MIM# 601780
Intellectual disability syndromic and non-syndromic v0.5992 CLN6 Zornitza Stark Mode of inheritance for gene: CLN6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5991 CLN6 Zornitza Stark reviewed gene: CLN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 6, MIM# 601780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5991 CLN3 Zornitza Stark Marked gene: CLN3 as ready
Intellectual disability syndromic and non-syndromic v0.5991 CLN3 Zornitza Stark Gene: cln3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5991 CLN3 Zornitza Stark Phenotypes for gene: CLN3 were changed from to Ceroid lipofuscinosis, neuronal, 3 MIM#204200
Intellectual disability syndromic and non-syndromic v0.5990 CLN3 Zornitza Stark Mode of inheritance for gene: CLN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5989 CLN3 Zornitza Stark reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 3 MIM#204200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5989 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Intellectual disability syndromic and non-syndromic v0.5989 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5989 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to CHARGE syndrome, MIM# 214800
Intellectual disability syndromic and non-syndromic v0.5988 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5987 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: CHARGE syndrome, MIM# 214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5987 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
Intellectual disability syndromic and non-syndromic v0.5987 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5987 CC2D2A Zornitza Stark Phenotypes for gene: CC2D2A were changed from to COACH syndrome 2, MIM# 619111; Joubert syndrome 9, MIM#612285; Meckel syndrome 6, MIM#612284
Intellectual disability syndromic and non-syndromic v0.5986 CC2D2A Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5985 CC2D2A Zornitza Stark reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: COACH syndrome 2, MIM# 619111, Joubert syndrome 9, 612285, Meckel syndrome 6, 612284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5985 CBL Zornitza Stark Marked gene: CBL as ready
Intellectual disability syndromic and non-syndromic v0.5985 CBL Zornitza Stark Gene: cbl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5985 CBL Zornitza Stark Mode of pathogenicity for gene: CBL was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.5985 CBL Zornitza Stark Phenotypes for gene: CBL were changed from to CBL-related disorder MONDO:0013308
Intellectual disability syndromic and non-syndromic v0.5984 CBL Zornitza Stark Publications for gene: CBL were set to
Intellectual disability syndromic and non-syndromic v0.5983 CBL Zornitza Stark Mode of inheritance for gene: CBL was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5982 CACNA1A Zornitza Stark Marked gene: CACNA1A as ready
Intellectual disability syndromic and non-syndromic v0.5982 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5982 CACNA1A Zornitza Stark Phenotypes for gene: CACNA1A were changed from to developmental and epileptic encephalopathy, 42 MONDO:0014917
Intellectual disability syndromic and non-syndromic v0.5981 CACNA1A Zornitza Stark Publications for gene: CACNA1A were set to
Intellectual disability syndromic and non-syndromic v0.5980 CACNA1A Zornitza Stark Mode of inheritance for gene: CACNA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5979 C12orf65 Zornitza Stark Marked gene: C12orf65 as ready
Intellectual disability syndromic and non-syndromic v0.5979 C12orf65 Zornitza Stark Gene: c12orf65 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5979 C12orf65 Zornitza Stark Phenotypes for gene: C12orf65 were changed from to hereditary spastic paraplegia 55 MONDO:0014020
Intellectual disability syndromic and non-syndromic v0.5978 C12orf65 Zornitza Stark Publications for gene: C12orf65 were set to
Intellectual disability syndromic and non-syndromic v0.5977 C12orf65 Zornitza Stark Mode of inheritance for gene: C12orf65 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5976 BTD Zornitza Stark Marked gene: BTD as ready
Intellectual disability syndromic and non-syndromic v0.5976 BTD Zornitza Stark Gene: btd has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5976 BTD Zornitza Stark Phenotypes for gene: BTD were changed from to biotinidase deficiency MONDO:0009665
Intellectual disability syndromic and non-syndromic v0.5975 BTD Zornitza Stark Publications for gene: BTD were set to
Intellectual disability syndromic and non-syndromic v0.5974 BTD Zornitza Stark Mode of inheritance for gene: BTD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5973 BSCL2 Zornitza Stark Marked gene: BSCL2 as ready
Intellectual disability syndromic and non-syndromic v0.5973 BSCL2 Zornitza Stark Gene: bscl2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5973 BSCL2 Zornitza Stark Phenotypes for gene: BSCL2 were changed from to congenital generalized lipodystrophy type 2 MONDO:0010020
Intellectual disability syndromic and non-syndromic v0.5972 BSCL2 Zornitza Stark Publications for gene: BSCL2 were set to
Intellectual disability syndromic and non-syndromic v0.5971 BSCL2 Zornitza Stark Mode of inheritance for gene: BSCL2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5970 BCS1L Zornitza Stark Marked gene: BCS1L as ready
Intellectual disability syndromic and non-syndromic v0.5970 BCS1L Zornitza Stark Gene: bcs1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5970 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from to Bjornstad syndrome MONDO:0009872
Intellectual disability syndromic and non-syndromic v0.5969 BCS1L Zornitza Stark Publications for gene: BCS1L were set to
Intellectual disability syndromic and non-syndromic v0.5968 BCS1L Zornitza Stark Mode of inheritance for gene: BCS1L was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5967 BCKDHB Zornitza Stark Marked gene: BCKDHB as ready
Intellectual disability syndromic and non-syndromic v0.5967 BCKDHB Zornitza Stark Gene: bckdhb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5967 BCKDHB Zornitza Stark Phenotypes for gene: BCKDHB were changed from to maple syrup urine disease type 1B MONDO:0023692
Intellectual disability syndromic and non-syndromic v0.5966 BCKDHB Zornitza Stark Publications for gene: BCKDHB were set to
Intellectual disability syndromic and non-syndromic v0.5965 BCKDHB Zornitza Stark Mode of inheritance for gene: BCKDHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5964 BCKDHA Zornitza Stark Marked gene: BCKDHA as ready
Intellectual disability syndromic and non-syndromic v0.5964 BCKDHA Zornitza Stark Gene: bckdha has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5964 BCKDHA Zornitza Stark Phenotypes for gene: BCKDHA were changed from to maple syrup urine disease type 1A MONDO:0023691
Intellectual disability syndromic and non-syndromic v0.5963 BCKDHA Zornitza Stark Publications for gene: BCKDHA were set to
Intellectual disability syndromic and non-syndromic v0.5962 BCKDHA Zornitza Stark Mode of inheritance for gene: BCKDHA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5961 BBS2 Zornitza Stark Marked gene: BBS2 as ready
Intellectual disability syndromic and non-syndromic v0.5961 BBS2 Zornitza Stark Gene: bbs2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5961 BBS2 Zornitza Stark Phenotypes for gene: BBS2 were changed from to Bardet-Biedl syndrome 2 MONDO:0014432
Intellectual disability syndromic and non-syndromic v0.5960 BBS2 Zornitza Stark Publications for gene: BBS2 were set to
Intellectual disability syndromic and non-syndromic v0.5959 BBS2 Zornitza Stark Mode of inheritance for gene: BBS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5958 BBS12 Zornitza Stark Marked gene: BBS12 as ready
Intellectual disability syndromic and non-syndromic v0.5958 BBS12 Zornitza Stark Gene: bbs12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5958 BBS12 Zornitza Stark Phenotypes for gene: BBS12 were changed from to Bardet-Biedl syndrome 12 MONDO:0014440
Intellectual disability syndromic and non-syndromic v0.5957 BBS12 Zornitza Stark Publications for gene: BBS12 were set to
Intellectual disability syndromic and non-syndromic v0.5956 BBS12 Zornitza Stark Mode of inheritance for gene: BBS12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5955 BBS10 Zornitza Stark Marked gene: BBS10 as ready
Intellectual disability syndromic and non-syndromic v0.5955 BBS10 Zornitza Stark Gene: bbs10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5955 BBS10 Zornitza Stark Phenotypes for gene: BBS10 were changed from to Bardet-Biedl syndrome 10 MONDO:0014438
Intellectual disability syndromic and non-syndromic v0.5954 BBS10 Zornitza Stark Publications for gene: BBS10 were set to
Intellectual disability syndromic and non-syndromic v0.5953 BBS10 Zornitza Stark Mode of inheritance for gene: BBS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5952 BBS1 Zornitza Stark Marked gene: BBS1 as ready
Intellectual disability syndromic and non-syndromic v0.5952 BBS1 Zornitza Stark Gene: bbs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5952 BBS1 Zornitza Stark Phenotypes for gene: BBS1 were changed from to Bardet-Biedl syndrome 1 MONDO:0008854
Intellectual disability syndromic and non-syndromic v0.5951 BBS1 Zornitza Stark Publications for gene: BBS1 were set to
Intellectual disability syndromic and non-syndromic v0.5950 BBS1 Zornitza Stark Mode of inheritance for gene: BBS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5949 TBCE Zornitza Stark Marked gene: TBCE as ready
Intellectual disability syndromic and non-syndromic v0.5949 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5949 TBCE Zornitza Stark Phenotypes for gene: TBCE were changed from to Encephalopathy, progressive, with amyotrophy and optic atrophy MIM:617207; Hypoparathyroidism-retardation-dysmorphism syndrome MIM:241410
Intellectual disability syndromic and non-syndromic v0.5948 TBCE Zornitza Stark Publications for gene: TBCE were set to
Intellectual disability syndromic and non-syndromic v0.5947 TBCE Zornitza Stark Mode of inheritance for gene: TBCE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5946 SLC25A1 Zornitza Stark Marked gene: SLC25A1 as ready
Intellectual disability syndromic and non-syndromic v0.5946 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5946 SLC25A1 Zornitza Stark Phenotypes for gene: SLC25A1 were changed from to Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072; Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596
Intellectual disability syndromic and non-syndromic v0.5945 SLC25A1 Zornitza Stark Publications for gene: SLC25A1 were set to
Intellectual disability syndromic and non-syndromic v0.5944 SLC25A1 Zornitza Stark Mode of inheritance for gene: SLC25A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5943 SLC25A1 Zornitza Stark reviewed gene: SLC25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072, Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5943 ROR2 Zornitza Stark Marked gene: ROR2 as ready
Intellectual disability syndromic and non-syndromic v0.5943 ROR2 Zornitza Stark Gene: ror2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5943 ROR2 Zornitza Stark Phenotypes for gene: ROR2 were changed from to Robinow syndrome, autosomal recessive, MIM#268310
Intellectual disability syndromic and non-syndromic v0.5942 ROR2 Zornitza Stark Publications for gene: ROR2 were set to 33937263, 32954672, 32172608
Intellectual disability syndromic and non-syndromic v0.5941 ROR2 Zornitza Stark Publications for gene: ROR2 were set to
Intellectual disability syndromic and non-syndromic v0.5940 ROR2 Zornitza Stark Mode of inheritance for gene: ROR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5939 ROR2 Zornitza Stark reviewed gene: ROR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Robinow syndrome, autosomal recessive, MIM#268310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5939 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Intellectual disability syndromic and non-syndromic v0.5939 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5939 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from to Peripheral demyelinating neuropathy Central demyelination, Waardenburg and Hirschsprung disease, OMIM #609136; Waardenburg syndrome, type 2E, with or without neurologic involvement (OMIM #611584)
Intellectual disability syndromic and non-syndromic v0.5938 SOX10 Zornitza Stark Publications for gene: SOX10 were set to
Intellectual disability syndromic and non-syndromic v0.5937 SOX10 Zornitza Stark Mode of inheritance for gene: SOX10 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5936 SLC4A4 Zornitza Stark Marked gene: SLC4A4 as ready
Intellectual disability syndromic and non-syndromic v0.5936 SLC4A4 Zornitza Stark Gene: slc4a4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5936 SLC4A4 Zornitza Stark Mode of inheritance for gene: SLC4A4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5935 SLC4A4 Zornitza Stark Mode of inheritance for gene: SLC4A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5934 SLC4A4 Zornitza Stark Publications for gene: SLC4A4 were set to
Intellectual disability syndromic and non-syndromic v0.5933 SLC4A4 Zornitza Stark Phenotypes for gene: SLC4A4 were changed from to Renal tubular acidosis, proximal, with ocular abnormalities MIM#604278
Intellectual disability syndromic and non-syndromic v0.5932 SLX4 Zornitza Stark Marked gene: SLX4 as ready
Intellectual disability syndromic and non-syndromic v0.5932 SLX4 Zornitza Stark Gene: slx4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5932 SLX4 Zornitza Stark Phenotypes for gene: SLX4 were changed from to Fanconi anaemia, complementation group P, MIM# 613951
Intellectual disability syndromic and non-syndromic v0.5931 SLX4 Zornitza Stark Publications for gene: SLX4 were set to
Intellectual disability syndromic and non-syndromic v0.5930 SLX4 Zornitza Stark Mode of inheritance for gene: SLX4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5929 SLX4 Zornitza Stark Classified gene: SLX4 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5929 SLX4 Zornitza Stark Gene: slx4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5928 SLX4 Zornitza Stark reviewed gene: SLX4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group P, MIM# 613951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5928 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Intellectual disability syndromic and non-syndromic v0.5928 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5928 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from to Developmental and epileptic encephalopathy 13, MIM# 614558
Intellectual disability syndromic and non-syndromic v0.5927 SCN8A Zornitza Stark Publications for gene: SCN8A were set to
Intellectual disability syndromic and non-syndromic v0.5926 SCN8A Zornitza Stark Mode of inheritance for gene: SCN8A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5925 THRA Zornitza Stark Marked gene: THRA as ready
Intellectual disability syndromic and non-syndromic v0.5925 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5925 THRA Zornitza Stark Phenotypes for gene: THRA were changed from to Hypothyroidism congenital nongoitrous 6 (MIM 614450)
Intellectual disability syndromic and non-syndromic v0.5924 THRA Zornitza Stark Publications for gene: THRA were set to
Intellectual disability syndromic and non-syndromic v0.5923 THRA Zornitza Stark Mode of inheritance for gene: THRA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5922 SIX3 Zornitza Stark Marked gene: SIX3 as ready
Intellectual disability syndromic and non-syndromic v0.5922 SIX3 Zornitza Stark Gene: six3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5922 SIX3 Zornitza Stark Phenotypes for gene: SIX3 were changed from to Holoprosencephaly 2, autosomal dominant, MIM#157170
Intellectual disability syndromic and non-syndromic v0.5921 SIX3 Zornitza Stark Publications for gene: SIX3 were set to
Intellectual disability syndromic and non-syndromic v0.5920 SIX3 Zornitza Stark Mode of inheritance for gene: SIX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5919 SIX3 Zornitza Stark reviewed gene: SIX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Holoprosencephaly 2, autosomal dominant, MIM#157170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5919 SAMHD1 Zornitza Stark Marked gene: SAMHD1 as ready
Intellectual disability syndromic and non-syndromic v0.5919 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5919 SAMHD1 Zornitza Stark Phenotypes for gene: SAMHD1 were changed from to Aicardi-Goutieres syndrome 5, MIM# 612952
Intellectual disability syndromic and non-syndromic v0.5918 SAMHD1 Zornitza Stark Publications for gene: SAMHD1 were set to
Intellectual disability syndromic and non-syndromic v0.5917 SAMHD1 Zornitza Stark Mode of inheritance for gene: SAMHD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5916 SCN2A Zornitza Stark Marked gene: SCN2A as ready
Intellectual disability syndromic and non-syndromic v0.5916 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5916 SCN2A Zornitza Stark Publications for gene: SCN2A were set to
Intellectual disability syndromic and non-syndromic v0.5915 SCN2A Zornitza Stark Phenotypes for gene: SCN2A were changed from to Developmental and epileptic encephalopathy 11, MIM# 613721
Intellectual disability syndromic and non-syndromic v0.5914 SCN2A Zornitza Stark Mode of inheritance for gene: SCN2A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5913 SCN2A Zornitza Stark Mode of inheritance for gene: SCN2A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5912 BMP4 Zornitza Stark Phenotypes for gene: BMP4 were changed from Microphthalmia, syndromic 6, MIM# 607932 to Microphthalmia, syndromic 6, MIM# 607932
Intellectual disability syndromic and non-syndromic v0.5911 BMP4 Zornitza Stark Marked gene: BMP4 as ready
Intellectual disability syndromic and non-syndromic v0.5911 BMP4 Zornitza Stark Gene: bmp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5911 BMP4 Zornitza Stark Phenotypes for gene: BMP4 were changed from to Microphthalmia, syndromic 6, MIM# 607932
Intellectual disability syndromic and non-syndromic v0.5910 BMP4 Zornitza Stark Publications for gene: BMP4 were set to
Intellectual disability syndromic and non-syndromic v0.5909 BMP4 Zornitza Stark Mode of inheritance for gene: BMP4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5908 BMP4 Zornitza Stark edited their review of gene: BMP4: Changed publications: 31053785
Intellectual disability syndromic and non-syndromic v0.5908 BMP4 Zornitza Stark reviewed gene: BMP4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microphthalmia, syndromic 6, MIM# 607932; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5908 CDON Zornitza Stark Marked gene: CDON as ready
Intellectual disability syndromic and non-syndromic v0.5908 CDON Zornitza Stark Gene: cdon has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5908 CDON Zornitza Stark Phenotypes for gene: CDON were changed from to holoprosencephaly 11 MONDO:0013642
Intellectual disability syndromic and non-syndromic v0.5907 CDON Zornitza Stark Publications for gene: CDON were set to
Intellectual disability syndromic and non-syndromic v0.5906 CDON Zornitza Stark Mode of inheritance for gene: CDON was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5905 RBBP8 Zornitza Stark Marked gene: RBBP8 as ready
Intellectual disability syndromic and non-syndromic v0.5905 RBBP8 Zornitza Stark Gene: rbbp8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5905 RBBP8 Zornitza Stark Phenotypes for gene: RBBP8 were changed from to Jawad syndrome, MIM#251255; Seckel syndrome 2, MIM#606744
Intellectual disability syndromic and non-syndromic v0.5904 RBBP8 Zornitza Stark Publications for gene: RBBP8 were set to
Intellectual disability syndromic and non-syndromic v0.5903 RBBP8 Zornitza Stark Mode of inheritance for gene: RBBP8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5902 RBBP8 Zornitza Stark reviewed gene: RBBP8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jawad syndrome, MIM#251255, Seckel syndrome 2, MIM#606744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5902 RBBP8 James The reviewed gene: RBBP8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30561437, 34270086, 32379725; Phenotypes: 606744, 251255, 113705; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5902 CDON Hali Van Niel reviewed gene: CDON: Rating: GREEN; Mode of pathogenicity: None; Publications: 21802063, 26728615, 31502381, 32729136, 26529631; Phenotypes: holoprosencephaly 11 MONDO:0013642; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5902 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Intellectual disability syndromic and non-syndromic v0.5902 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5902 SAMD9 Zornitza Stark Phenotypes for gene: SAMD9 were changed from MIRAGE Syndrome, MIM#617053 to MIRAGE Syndrome, MIM#617053
Intellectual disability syndromic and non-syndromic v0.5901 SAMD9 Zornitza Stark Phenotypes for gene: SAMD9 were changed from to MIRAGE Syndrome, MIM#617053
Intellectual disability syndromic and non-syndromic v0.5900 SAMD9 Zornitza Stark Publications for gene: SAMD9 were set to
Intellectual disability syndromic and non-syndromic v0.5899 SAMD9 Zornitza Stark Mode of inheritance for gene: SAMD9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5898 SAMD9 Zornitza Stark reviewed gene: SAMD9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MIRAGE Syndrome, MIM#617053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5898 BMP4 Hali Van Niel reviewed gene: BMP4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22581619, 31053785, 30568244, 18252212, 21340693, 34926457, 36140739, 37107605; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5898 LIG4 Zornitza Stark Marked gene: LIG4 as ready
Intellectual disability syndromic and non-syndromic v0.5898 LIG4 Zornitza Stark Gene: lig4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5898 LIG4 Zornitza Stark Publications for gene: LIG4 were set to
Intellectual disability syndromic and non-syndromic v0.5897 LIG4 Zornitza Stark Phenotypes for gene: LIG4 were changed from to LIG4 syndrome, MIM# 606593
Intellectual disability syndromic and non-syndromic v0.5896 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5895 LIG4 Zornitza Stark Mode of inheritance for gene: LIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5894 SLC35A1 Zornitza Stark Marked gene: SLC35A1 as ready
Intellectual disability syndromic and non-syndromic v0.5894 SLC35A1 Zornitza Stark Gene: slc35a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5894 SLC35A1 Zornitza Stark Phenotypes for gene: SLC35A1 were changed from to Congenital disorder of glycosylation, type IIf, MIM# 603585
Intellectual disability syndromic and non-syndromic v0.5893 SLC35A1 Zornitza Stark Publications for gene: SLC35A1 were set to
Intellectual disability syndromic and non-syndromic v0.5892 SLC35A1 Zornitza Stark Mode of inheritance for gene: SLC35A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5891 SLC35A1 Zornitza Stark Classified gene: SLC35A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5891 SLC35A1 Zornitza Stark Gene: slc35a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5890 SLC35A1 Zornitza Stark edited their review of gene: SLC35A1: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.5890 SLC35A1 Zornitza Stark changed review comment from: At least 3 families reported.; to: At least 3 families reported, neurological presentation in two.
Intellectual disability syndromic and non-syndromic v0.5890 SLC35A1 Zornitza Stark reviewed gene: SLC35A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28856833, 23873973, 11157507; Phenotypes: Congenital disorder of glycosylation, type IIf, MIM# 603585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5890 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Intellectual disability syndromic and non-syndromic v0.5890 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5890 LRPPRC Zornitza Stark Phenotypes for gene: LRPPRC were changed from to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian), MIM#220111
Intellectual disability syndromic and non-syndromic v0.5889 LRPPRC Zornitza Stark Publications for gene: LRPPRC were set to
Intellectual disability syndromic and non-syndromic v0.5888 LRPPRC Zornitza Stark Mode of inheritance for gene: LRPPRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5887 LRPPRC Zornitza Stark reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian), MIM#220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5887 TREX1 Zornitza Stark Marked gene: TREX1 as ready
Intellectual disability syndromic and non-syndromic v0.5887 TREX1 Zornitza Stark Gene: trex1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5887 TREX1 Zornitza Stark Phenotypes for gene: TREX1 were changed from to Aicardi-Goutieres syndrome MONDO:0018866
Intellectual disability syndromic and non-syndromic v0.5886 TREX1 Zornitza Stark Publications for gene: TREX1 were set to
Intellectual disability syndromic and non-syndromic v0.5885 TREX1 Zornitza Stark Mode of inheritance for gene: TREX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5884 SERAC1 Zornitza Stark Marked gene: SERAC1 as ready
Intellectual disability syndromic and non-syndromic v0.5884 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5884 SERAC1 Zornitza Stark Phenotypes for gene: SERAC1 were changed from to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL), MIM#614739
Intellectual disability syndromic and non-syndromic v0.5883 SERAC1 Zornitza Stark Publications for gene: SERAC1 were set to
Intellectual disability syndromic and non-syndromic v0.5883 SERAC1 Zornitza Stark Mode of inheritance for gene: SERAC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5882 SERAC1 Zornitza Stark Mode of inheritance for gene: SERAC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SERAC1 Zornitza Stark reviewed gene: SERAC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24741715, 37711114, 37090937, 28916646, 32684373; Phenotypes: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL), MIM#614739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 TREX1 Hali Van Niel changed review comment from: Established gene disease association with Aicardi-Goutières Syndrome
Heterogeneity with variable phenotype, ranges from preserved cognition to severe intellectual disability
TREX1-related Aicardi Goutières syndrome have higher impairment (31559893)
ID common presenting feature (PMID: 25604658); to: Established gene disease association with Aicardi-Goutières Syndrome
Heterogeneity with variable phenotype, ranges from preserved cognition to severe intellectual disability
TREX1-related Aicardi Goutières syndrome have higher impairment (PMID: 31559893)
ID common presenting feature (PMID: 25604658)
Intellectual disability syndromic and non-syndromic v0.5881 TREX1 Hali Van Niel edited their review of gene: TREX1: Changed publications: 25604658, 16845398, 17357087, 31559893
Intellectual disability syndromic and non-syndromic v0.5881 TREX1 Hali Van Niel reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25604658, 16845398, 17357087; Phenotypes: Aicardi-Goutieres syndrome MONDO:0018866; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 LRPPRC Kirsty Choi reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21266382, 8392290, 8392291, 26510951; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian), 220111, developmental delay, hypotonia, mild facial dysmorphism, chronic well-compensated metabolic acidosis, high mortality due to episodes of severe acidosis and coma, hypertension, cerebrospinal fluid lactate levels, decreased blood bicarbonate levels, microvesicular steatosis, psychomotor delay, ataxia, hypotonia, transient tachypnea of the newborn, poor sucking, tremor, hypoglycemia, seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SLC35A1 Anissa Johnson changed review comment from: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".
AR inheritance.; to: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents, consanguineous, were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".
AR inheritance.
Intellectual disability syndromic and non-syndromic v0.5881 SLC35A1 Anissa Johnson changed review comment from: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".; to: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".
AR inheritance.
Intellectual disability syndromic and non-syndromic v0.5881 SLC35A1 Anissa Johnson commented on gene: SLC35A1: PMID: 23873973: 1 patient identified, homozygous with a variant in SLC35A1. Parents were heterozygous for the variant. Presented with "intellectual disability, seizures, ataxia, macrothrombocytopaenia, renal and cardiac involvement, and abnormal protein glycosylation". Biochemical assay showed "combined N- and O-glycosylation abnormalities and specific reduction in sialylation".
Intellectual disability syndromic and non-syndromic v0.5881 SLC35A1 Anissa Johnson reviewed gene: SLC35A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23873973; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 LIG4 Santosh Varughese reviewed gene: LIG4: 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: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302; Phenotypes: lIG4 syndrome, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SAMD9 Raluca Rusu reviewed gene: SAMD9: Rating: RED; Mode of pathogenicity: Other; Publications: PMID: 27182967, 34659124, 32194975, 29175836, 37195360, 30900330, 37745698; Phenotypes: MIRAGE Syndrome, MIM#617053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5881 SCN2A sabitha sateesh reviewed gene: SCN2A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31230762, 31904126, 28256214, 31904120, 31924505, 31205438, 1325650, 17021166; Phenotypes: Intellectual disability, autism, motor delay, epileptic seizures, uncoordinated oral movements, gastrointestinal disturbances, sleep problems.; Mode of inheritance: Unknown; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5881 SAMHD1 Reetoo Ramessur reviewed gene: SAMHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301648, 29239743, 25246298, 19525956, 21102625, 33307271, 35418820; Phenotypes: Aicardi-Goutieres syndrome 5, MIM# 612952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SIX3 Laura Mazurkijevic reviewed gene: SIX3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20531442, 19346217, 20157829, 15635066; Phenotypes: Holoprosencephaly 2, autosomal dominant, MIM#157170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5881 THRA Hnin Aung changed review comment from: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].; to: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestations for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].
Intellectual disability syndromic and non-syndromic v0.5881 THRA Hnin Aung changed review comment from: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].; to: Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestation for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].
Intellectual disability syndromic and non-syndromic v0.5881 THRA Hnin Aung reviewed gene: THRA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22494134, 23940126, 24847461, 25670821, 26037512, 25621899, 27144938, 28856816, 30842990, 37469961; Phenotypes: Hypothyroidism congenital nongoitrous 6 (MIM 614450), Intellectual disability syndromic, Growth retardation, Facial dysmorphism, Constipation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5881 SCN8A Tinashe Nhindiri reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34353676, 38233770, 30171078; Phenotypes: Epileptic encephalopathy, Developmental delay, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5881 SLX4 Lovepreet Gill reviewed gene: SLX4: Rating: RED; 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: 21240277, 21240275, 23093618, 26453996); Phenotypes: Franconia anemia, complementation group P; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5881 SLC4A4 Adam Ivey reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29914390, 11274232, 15930088; Phenotypes: OMIM:604278-RENAL TUBULAR ACIDOSIS, PROXIMAL, WITH OCULAR ABNORMALITIES AND IMPAIRED INTELLECTUAL DEVELOPMENT; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SOX10 David Fairbairn changed review comment from: Main mutation mechanism: truncated proteins, potent dominant-negative activity and more severe phenotype only when escapes NMD. Decipher: SOX 10 copy number losses and gains associated with intellectual disability. PCWH Gene2Phenotype: monoallelic-altered gene product structure, DD definitive. Waardenburg syndrome, type 2E Gene2Phenotype: monoallelic-absent gene product, DD definitive. GenCC definitive. OMIM #609136: dominant-negative heterozygous SOX 10 variants in multiple (>3) unrelated cases resulting in neurologic features.; to: Main mutation mechanism: truncated proteins, potent dominant-negative activity and more severe phenotype only when escapes NMD. Decipher: SOX 10 copy number losses and gains associated with intellectual disability. PCWH Gene2Phenotype: monoallelic-altered gene product structure, DD definitive. Waardenburg syndrome, type 2E Gene2Phenotype: monoallelic-absent gene product, DD definitive. GenCC definitive. OMIM #609136: dominant-negative heterozygous SOX 10 variants in multiple (>3) unrelated cases resulting in neurologic features.
Intellectual disability syndromic and non-syndromic v0.5881 SOX10 David Fairbairn reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10762540, 34667088, 38132479; Phenotypes: PCWH (Peripheral demyelinating neuropathy Central demyelination, Waardenburg and Hirschsprung disease) syndrome (OMIM #609136), Waardenburg syndrome, type 2E, with or without neurologic involvement (OMIM #611584); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5881 ROR2 Shani Stuart reviewed gene: ROR2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 33937263, 32954672, 32172608; Phenotypes: Intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SLC25A1 Alyson Lewis reviewed gene: SLC25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31527857, PMID: 26870663; Phenotypes: Impaired intellectual development, mild, Learning disabilities, Delayed motor development; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 TBCE Leanne Baxter reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:27666369: PMID:17699660: PMID:34356170: PMID: 34134906; Phenotypes: Encephalopathy, progressive, with amyotrophy and optic atrophy MIM:617207, Hypoparathyroidism-retardation-dysmorphism syndrome MIM:241410, Kenny-Caffey syndrome, type 1 MIM:244460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5881 SLC19A3 Zornitza Stark Marked gene: SLC19A3 as ready
Intellectual disability syndromic and non-syndromic v0.5881 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5881 SLC19A3 Zornitza Stark Publications for gene: SLC19A3 were set to
Intellectual disability syndromic and non-syndromic v0.5880 SLC19A3 Zornitza Stark Phenotypes for gene: SLC19A3 were changed from to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483
Intellectual disability syndromic and non-syndromic v0.5879 SLC19A3 Zornitza Stark Mode of inheritance for gene: SLC19A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5878 SPECC1L Zornitza Stark Marked gene: SPECC1L as ready
Intellectual disability syndromic and non-syndromic v0.5878 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5878 SLC19A3 Jane Lin changed review comment from: Rare disorder of thiamine metabolism and transport. Has well characterised gene-phenotype link in more than 3 families (multiple publications, in different subpopulations). Many symptoms in this disorder, for example confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and dysphagia. ID has been described as a sequela in many cases.; to: Rare disorder of thiamine metabolism and transport. Has well characterised gene-phenotype link for THMD2 in more than 3 families (multiple publications, in different subpopulations). Many CNS related symptoms in this disorder, for example confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and dysphagia. ID has been described as a sequela in many cases.
Intellectual disability syndromic and non-syndromic v0.5878 SLC19A3 Jane Lin reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15871139, PMID: 34276785, PMID: 23482991, PMID: 20065143; Phenotypes: # 607483 BASAL GANGLIA DISEASE, BIOTIN-THIAMINE RESPONSIVE (BBTGD), THIAMINE METABOLISM DYSFUNCTION SYNDROME 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5878 SASS6 Zornitza Stark Marked gene: SASS6 as ready
Intellectual disability syndromic and non-syndromic v0.5878 SASS6 Zornitza Stark Gene: sass6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5878 SASS6 Zornitza Stark Classified gene: SASS6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5878 SASS6 Zornitza Stark Gene: sass6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5877 SASS6 Zornitza Stark gene: SASS6 was added
gene: SASS6 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: SASS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SASS6 were set to 24951542; 30639237
Phenotypes for gene: SASS6 were set to Microcephaly 14, primary, autosomal recessive, MIM# 616402
Review for gene: SASS6 was set to GREEN
Added comment: At least 3 unrelated families reported, severe ID is part of the phenotype.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5876 SPECC1L Zornitza Stark Phenotypes for gene: SPECC1L were changed from to Teebi hypertelorism syndrome 1, MIM# 145420
Intellectual disability syndromic and non-syndromic v0.5875 SPECC1L Zornitza Stark Publications for gene: SPECC1L were set to
Intellectual disability syndromic and non-syndromic v0.5874 SPECC1L Zornitza Stark Mode of inheritance for gene: SPECC1L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5873 SPECC1L Zornitza Stark reviewed gene: SPECC1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Teebi hypertelorism syndrome 1, MIM# 145420; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5873 SPECC1L Ibrahim El-Deek changed review comment from: There is paucity of literature directly linking SPECC1L variants to intellectual disability and developmental delay. However, Zhang et al. (PMID: 31953237) reviewed 33 patients from 14 families with SPECC1L variants, noting that the most common features were dysmorphic facial characteristics. Developmental delays were reported in 24.2% of patients (8/33), with some achieving normal development during childhood.; to: There is paucity of literature directly linking SPECC1L variants to intellectual disability and developmental delay. However, Zhang et al. (PMID: 31953237) reviewed 33 patients from 14 families with SPECC1L variants (including 10 missense point mutation and 1 deletion), noting that the most common features were dysmorphic facial characteristics. Developmental delays were reported in 24.2% of patients (8/33), with some achieving normal development during childhood.
Intellectual disability syndromic and non-syndromic v0.5873 SPECC1L Ibrahim El-Deek reviewed gene: SPECC1L: Rating: RED; Mode of pathogenicity: Other; Publications: 31953237, 30472488; Phenotypes: Teebi hypertelorism syndrome 1, Oblique Facial Clefting 1, Opitz GBBB syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5873 GABRA4 Adam Ivey gene: GABRA4 was added
gene: GABRA4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GABRA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRA4 were set to PMID: 38565639
Phenotypes for gene: GABRA4 were set to Developmental delay; Intellectual disability; Epileptic seizures
Penetrance for gene: GABRA4 were set to Complete
Review for gene: GABRA4 was set to GREEN
Added comment: Four unrelated individuals with unique de novo missense variants in the transmembrane domain of GABRA4 have developmental delay and varying degrees of intellectual disability (PMID: 38565639). These variants are not present in gnomAD and three of the four variants have pathogenic REVEL scores. Two of the GABRA4 variants were heterozygous, while the remaining two were mosaic.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5873 L1CAM Zornitza Stark Marked gene: L1CAM as ready
Intellectual disability syndromic and non-syndromic v0.5873 L1CAM Zornitza Stark Gene: l1cam has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5873 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from to L1 syndrome MONDO:0017140
Intellectual disability syndromic and non-syndromic v0.5872 L1CAM Zornitza Stark Mode of inheritance for gene: L1CAM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5871 LAMC3 Zornitza Stark Marked gene: LAMC3 as ready
Intellectual disability syndromic and non-syndromic v0.5871 LAMC3 Zornitza Stark Gene: lamc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5871 LAMC3 Zornitza Stark Phenotypes for gene: LAMC3 were changed from to complex neurodevelopmental disorder MONDO:0100038; Cortical malformations, occipital, MIM# 614115
Intellectual disability syndromic and non-syndromic v0.5870 LAMC3 Zornitza Stark Publications for gene: LAMC3 were set to
Intellectual disability syndromic and non-syndromic v0.5869 LAMC3 Zornitza Stark Mode of inheritance for gene: LAMC3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5868 LAMC3 Zornitza Stark Classified gene: LAMC3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5868 LAMC3 Zornitza Stark Gene: lamc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5867 LAMC3 Zornitza Stark reviewed gene: LAMC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 38758065, 21572413; Phenotypes: complex neurodevelopmental disorder MONDO:0100038, Cortical malformations, occipital, MIM# 614115; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5867 MAGT1 Zornitza Stark Phenotypes for gene: MAGT1 were changed from Congenital disorder of glycosylation, type Icc, OMIM #301031; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia, OMIM #300853 to X-linked intellectual disability MONDO:0100284; Congenital disorder of glycosylation, type Icc, OMIM #301031
Intellectual disability syndromic and non-syndromic v0.5866 MAGT1 Zornitza Stark Classified gene: MAGT1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5866 MAGT1 Zornitza Stark Gene: magt1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5865 MAGT1 Zornitza Stark Tag disputed tag was added to gene: MAGT1.
Intellectual disability syndromic and non-syndromic v0.5865 MBTPS2 Zornitza Stark Marked gene: MBTPS2 as ready
Intellectual disability syndromic and non-syndromic v0.5865 MBTPS2 Zornitza Stark Gene: mbtps2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5865 MBTPS2 Zornitza Stark Phenotypes for gene: MBTPS2 were changed from to IFAP syndrome 1, with or without BRESHECK syndrome MONDO:0100213
Intellectual disability syndromic and non-syndromic v0.5864 MBTPS2 Zornitza Stark Mode of inheritance for gene: MBTPS2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5863 MED12 Zornitza Stark Marked gene: MED12 as ready
Intellectual disability syndromic and non-syndromic v0.5863 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5863 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from to MED12-related intellectual disability syndrome MONDO:0100000
Intellectual disability syndromic and non-syndromic v0.5862 MED12 Zornitza Stark Mode of inheritance for gene: MED12 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5861 MED13L Zornitza Stark Marked gene: MED13L as ready
Intellectual disability syndromic and non-syndromic v0.5861 MED13L Zornitza Stark Gene: med13l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5861 MED13L Zornitza Stark Phenotypes for gene: MED13L were changed from to syndromic intellectual disability MONDO:0000508
Intellectual disability syndromic and non-syndromic v0.5860 MED13L Zornitza Stark Publications for gene: MED13L were set to
Intellectual disability syndromic and non-syndromic v0.5859 MED13L Zornitza Stark Mode of inheritance for gene: MED13L was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5858 MED23 Zornitza Stark Marked gene: MED23 as ready
Intellectual disability syndromic and non-syndromic v0.5858 MED23 Zornitza Stark Gene: med23 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5858 MED23 Zornitza Stark Phenotypes for gene: MED23 were changed from to syndromic intellectual disability MONDO:0000508
Intellectual disability syndromic and non-syndromic v0.5857 MED23 Zornitza Stark Publications for gene: MED23 were set to
Intellectual disability syndromic and non-syndromic v0.5856 MED23 Zornitza Stark Mode of inheritance for gene: MED23 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5855 MID1 Zornitza Stark Marked gene: MID1 as ready
Intellectual disability syndromic and non-syndromic v0.5855 MID1 Zornitza Stark Gene: mid1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5855 MID1 Zornitza Stark Phenotypes for gene: MID1 were changed from to X-linked Opitz G/BBB syndrome MONDO:0010222
Intellectual disability syndromic and non-syndromic v0.5854 MID1 Zornitza Stark Mode of inheritance for gene: MID1 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5853 NDP Zornitza Stark Marked gene: NDP as ready
Intellectual disability syndromic and non-syndromic v0.5853 NDP Zornitza Stark Gene: ndp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5853 NDP Zornitza Stark Phenotypes for gene: NDP were changed from to Norrie disease MONDO:0010691
Intellectual disability syndromic and non-syndromic v0.5852 NDP Zornitza Stark Mode of inheritance for gene: NDP was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5851 NSD1 Zornitza Stark Marked gene: NSD1 as ready
Intellectual disability syndromic and non-syndromic v0.5851 NSD1 Zornitza Stark Gene: nsd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5851 NSD1 Zornitza Stark Phenotypes for gene: NSD1 were changed from to Sotos syndrome MONDO:0019349
Intellectual disability syndromic and non-syndromic v0.5850 NSD1 Zornitza Stark Mode of inheritance for gene: NSD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5849 OCRL Zornitza Stark Marked gene: OCRL as ready
Intellectual disability syndromic and non-syndromic v0.5849 OCRL Zornitza Stark Gene: ocrl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5849 OCRL Zornitza Stark Phenotypes for gene: OCRL were changed from to oculocerebrorenal syndrome MONDO:0010645
Intellectual disability syndromic and non-syndromic v0.5848 OCRL Zornitza Stark Mode of inheritance for gene: OCRL was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5847 OFD1 Zornitza Stark Marked gene: OFD1 as ready
Intellectual disability syndromic and non-syndromic v0.5847 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5847 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to ciliopathy MONDO:0005308
Intellectual disability syndromic and non-syndromic v0.5846 OFD1 Zornitza Stark Publications for gene: OFD1 were set to
Intellectual disability syndromic and non-syndromic v0.5845 OFD1 Zornitza Stark Mode of inheritance for gene: OFD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5844 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Intellectual disability syndromic and non-syndromic v0.5844 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5844 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from to Pelizeaus-Merzbacher spectrum disorder MONDO:0010714
Intellectual disability syndromic and non-syndromic v0.5843 PLP1 Zornitza Stark Mode of inheritance for gene: PLP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5842 PORCN Zornitza Stark Marked gene: PORCN as ready
Intellectual disability syndromic and non-syndromic v0.5842 PORCN Zornitza Stark Gene: porcn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5842 PORCN Zornitza Stark Phenotypes for gene: PORCN were changed from to focal dermal hypoplasia MONDO:0010592
Intellectual disability syndromic and non-syndromic v0.5841 PORCN Zornitza Stark Publications for gene: PORCN were set to
Intellectual disability syndromic and non-syndromic v0.5840 PORCN Zornitza Stark Mode of inheritance for gene: PORCN was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5839 PTCHD1 Zornitza Stark Marked gene: PTCHD1 as ready
Intellectual disability syndromic and non-syndromic v0.5839 PTCHD1 Zornitza Stark Gene: ptchd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5839 PTCHD1 Zornitza Stark Phenotypes for gene: PTCHD1 were changed from to non-syndromic X-linked intellectual disability MONDO:0019181
Intellectual disability syndromic and non-syndromic v0.5838 PTCHD1 Zornitza Stark Mode of inheritance for gene: PTCHD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5837 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5837 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5837 SETBP1 Zornitza Stark Phenotypes for gene: SETBP1 were changed from to Schinzel-Giedion syndrome MONDO:0010010; complex neurodevelopmental disorder MONDO:0100038
Intellectual disability syndromic and non-syndromic v0.5836 SETBP1 Zornitza Stark Publications for gene: SETBP1 were set to
Intellectual disability syndromic and non-syndromic v0.5835 SETBP1 Zornitza Stark Mode of inheritance for gene: SETBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5834 SHROOM4 Zornitza Stark Classified gene: SHROOM4 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5834 SHROOM4 Zornitza Stark Gene: shroom4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5833 SHROOM4 Zornitza Stark Tag disputed tag was added to gene: SHROOM4.
Intellectual disability syndromic and non-syndromic v0.5833 SLC25A15 Zornitza Stark Marked gene: SLC25A15 as ready
Intellectual disability syndromic and non-syndromic v0.5833 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5833 SLC25A15 Zornitza Stark Phenotypes for gene: SLC25A15 were changed from to Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, MIM#238970
Intellectual disability syndromic and non-syndromic v0.5832 SLC25A15 Zornitza Stark Publications for gene: SLC25A15 were set to
Intellectual disability syndromic and non-syndromic v0.5831 SLC25A15 Zornitza Stark Mode of inheritance for gene: SLC25A15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5830 SLC6A4 Zornitza Stark Phenotypes for gene: SLC6A4 were changed from {Obsessive-compulsive disorder}, MIM# 164230; depression; alcohol dependence to autism spectrum disorder MONDO:0005258; {Obsessive-compulsive disorder}, MIM# 164230
Intellectual disability syndromic and non-syndromic v0.5829 SLC6A4 Zornitza Stark Tag disputed tag was added to gene: SLC6A4.
Intellectual disability syndromic and non-syndromic v0.5829 WAC Zornitza Stark Publications for gene: WAC were set to 26264232
Intellectual disability syndromic and non-syndromic v0.5828 ZDHHC15 Zornitza Stark Phenotypes for gene: ZDHHC15 were changed from Mental retardation, X-linked 91, 300577 to Intellectual disability, X-linked 91, 300577
Intellectual disability syndromic and non-syndromic v0.5827 ZDHHC15 Zornitza Stark Tag disputed tag was added to gene: ZDHHC15.
Intellectual disability syndromic and non-syndromic v0.5827 ZNF41 Zornitza Stark Phenotypes for gene: ZNF41 were changed from to non-syndromic X-linked intellectual disability MONDO:0019181
Intellectual disability syndromic and non-syndromic v0.5826 ZNF41 Zornitza Stark Mode of inheritance for gene: ZNF41 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5825 ZNF41 Zornitza Stark Tag disputed tag was added to gene: ZNF41.
Intellectual disability syndromic and non-syndromic v0.5825 ZNF674 Zornitza Stark Tag disputed tag was added to gene: ZNF674.
Intellectual disability syndromic and non-syndromic v0.5825 ZNF81 Zornitza Stark Phenotypes for gene: ZNF81 were changed from Intellectual disability to X-linked intellectual disability MONDO:0100284
Intellectual disability syndromic and non-syndromic v0.5824 SHANK2 Zornitza Stark Marked gene: SHANK2 as ready
Intellectual disability syndromic and non-syndromic v0.5824 SHANK2 Zornitza Stark Gene: shank2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5824 SHANK2 Zornitza Stark Phenotypes for gene: SHANK2 were changed from to Autism, susceptibility to, 17, MIM#613436; complex neurodevelopmental disorder MONDO:0100038
Intellectual disability syndromic and non-syndromic v0.5823 SHANK2 Zornitza Stark Publications for gene: SHANK2 were set to
Intellectual disability syndromic and non-syndromic v0.5822 SHANK2 Zornitza Stark Mode of inheritance for gene: SHANK2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 SHANK2 Zornitza Stark reviewed gene: SHANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 SHANK2 Aaron Meyers reviewed gene: SHANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20473310, 22346768, 20531469, 35456494, 32987185, 25188300, 22699619, 22699620; Phenotypes: Autism, susceptibility to, 17, MIM#613436, Autism spectrum disorder; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 ZNF81 Sangavi Sivagnanasundram reviewed gene: ZNF81: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006590; Phenotypes: X-linked intellectual disability MONDO:0100284; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 ZNF674 Sangavi Sivagnanasundram reviewed gene: ZNF674: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006588; Phenotypes: X-linked intellectual disability MONDO:0100284; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 ZNF41 Sangavi Sivagnanasundram reviewed gene: ZNF41: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006585; Phenotypes: non-syndromic X-linked intellectual disability MONDO:0019181; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 ZDHHC15 Sangavi Sivagnanasundram reviewed gene: ZDHHC15: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006573; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 WAC Sangavi Sivagnanasundram reviewed gene: WAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26757981, https://search.clinicalgenome.org/CCID:006532; Phenotypes: DeSanto-Shinawi syndrome MONDO:0018760; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 TCF7L2 Sangavi Sivagnanasundram reviewed gene: TCF7L2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006339; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 SLC6A4 Sangavi Sivagnanasundram changed review comment from: DISPUTED classification by ClinGen ID and Autism GCEP on 06/01/2021 due to variants association with ASD having high frequencies in gnomAD - https://search.clinicalgenome.org/CCID:006198; to: DISPUTED classification by ClinGen ID and Autism GCEP on 06/01/2021. Variants in this gene associated with ASD having high frequencies in gnomAD - https://search.clinicalgenome.org/CCID:006198
Intellectual disability syndromic and non-syndromic v0.5821 SLC6A4 Sangavi Sivagnanasundram reviewed gene: SLC6A4: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006198; Phenotypes: autism spectrum disorder MONDO:0005258; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 SLC25A15 Rajkumar Krishnaswamy changed review comment from: Rare genetic disorder representing a heterogeneous disease with high clinical variability. Pyramidal dysfunction, developmental, cognitive and behavioural abnormalities have been reported. ID/mental retardation ranging from mild, moderate to severe have been reported in several cases usually manifesting in the childhood or as adult onset.; to: Rare genetic disorder representing a heterogeneous disease with high clinical variability. Lethargy, feeding difficulties, seizures, pyramidal dysfunction, developmental, cognitive and behavioural abnormalities have been reported with various features exhibited at various stages of life e.g. neonates, infantile/childhood and adults.
ID/mental retardation ranging from mild, moderate to severe have been reported in several cases usually manifesting in childhood or adults.
Intellectual disability syndromic and non-syndromic v0.5821 SHROOM4 Sangavi Sivagnanasundram reviewed gene: SHROOM4: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:006141; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram reviewed gene: SETBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28346496, 21037274; Phenotypes: Schinzel-Giedion syndrome MONDO:0010010, complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 SLC25A15 Rajkumar Krishnaswamy reviewed gene: SLC25A15: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18978333, 25874378; Phenotypes: Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, 238970, hyperammonemia, lethargy, somnolence, refusal to feed, vomiting, tachypnea with respiratory alkalosis, seizures, protein intolerance, developmental delay, spasticity, intellectual disability / mental retardation, dysarthria, learning disabilities, spasticity, liver dysfunction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram Deleted their review
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram commented on gene: SETBP1: Classified DEFINITIVE for both conditions by ClinGen ID and Autism GCEP.

SGS classified on 16/02/2021 - https://search.clinicalgenome.org/CCID:006117
Complex neurodevelopmental disorders on 20/10/2020 - https://search.clinicalgenome.org/CCID:006116

LoF is associated with complex neurodevelopmental disorder. There have been 20 LoF variants reported in individuals so far (nonsense, frameshift, large deletions)

GoF is proposed to be the mechanism of disease for Schinzel-Giedion syndrome (SGS) due to an increase in SETBP1 protein production. Missense variants (especially affecting p.868-871) are known to be disease causing.
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram commented on gene: SETBP1: Classified DEFINITIVE for both conditions by ClinGen ID and Autism GCEP.

SGS classified on 16/02/2021 - https://search.clinicalgenome.org/CCID:006117
Complex neurodevelopmental disorders on 20/10/2020 - https://search.clinicalgenome.org/CCID:006116

LoF is associated with complex neurodevelopmental disorder. There have been 20 LoF variants reported in individuals so far (nonsense, frameshift, large deletions)

GoF is proposed to be the mechanism of disease for Schinzel-Giedion syndrome (SGS) due to an increase in SETBP1 protein production. Missense variants (especially affecting p.868-871) are known to be disease causing.
Intellectual disability syndromic and non-syndromic v0.5821 SETBP1 Sangavi Sivagnanasundram reviewed gene: SETBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28346496, 21037274; Phenotypes: Schinzel-Giedion syndrome MONDO:0010010, complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 PTCHD1 Sangavi Sivagnanasundram reviewed gene: PTCHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005921; Phenotypes: non-syndromic X-linked intellectual disability MONDO:0019181; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 PORCN Sangavi Sivagnanasundram reviewed gene: PORCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301712; Phenotypes: focal dermal hypoplasia MONDO:0010592; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 PLP1 Sangavi Sivagnanasundram reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: https://search.clinicalgenome.org/CCID:005834; Phenotypes: Pelizeaus-Merzbacher spectrum disorder MONDO:0010714; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 OFD1 Sangavi Sivagnanasundram reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24884629; Phenotypes: ciliopathy MONDO:0005308; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 OCRL Sangavi Sivagnanasundram reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005696; Phenotypes: oculocerebrorenal syndrome MONDO:0010645; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 NSD1 Sangavi Sivagnanasundram reviewed gene: NSD1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005680; Phenotypes: Sotos syndrome MONDO:0019349; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 NDP Sangavi Sivagnanasundram edited their review of gene: NDP: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.5821 NDP Sangavi Sivagnanasundram reviewed gene: NDP: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005574; Phenotypes: Norrie disease MONDO:0010691; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 MID1 Sangavi Sivagnanasundram reviewed gene: MID1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005386; Phenotypes: X-linked Opitz G/BBB syndrome MONDO:0010222; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 MED23 Sangavi Sivagnanasundram reviewed gene: MED23: Rating: GREEN; Mode of pathogenicity: None; Publications: 21868677, 25845469, 27311965, 27457812, 30847200, 31164858; Phenotypes: syndromic intellectual disability MONDO:0000508; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5821 MED13L Sangavi Sivagnanasundram reviewed gene: MED13L: Rating: GREEN; Mode of pathogenicity: None; Publications: 28645799, 29511999; Phenotypes: syndromic intellectual disability MONDO:0000508; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 MED12 Sangavi Sivagnanasundram reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005361; Phenotypes: MED12-related intellectual disability syndrome MONDO:0100000; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 MBTPS2 Sangavi Sivagnanasundram reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005345; Phenotypes: IFAP syndrome 1, with or without BRESHECK syndrome MONDO:0100213; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 MAN1B1 Sangavi Sivagnanasundram reviewed gene: MAN1B1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: MAN1B1-congenital disorder of glycosylation MONDO:0018349; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5821 MAGT1 Sangavi Sivagnanasundram reviewed gene: MAGT1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005319; Phenotypes: X-linked intellectual disability MONDO:0100284; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 LAMC3 Sangavi Sivagnanasundram reviewed gene: LAMC3: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005265; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 L1CAM Sangavi Sivagnanasundram reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005260; Phenotypes: L1 syndrome MONDO:0017140; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 KIRREL3 Sangavi Sivagnanasundram reviewed gene: KIRREL3: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005235; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 KATNAL2 Sangavi Sivagnanasundram reviewed gene: KATNAL2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005176; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 KAT6B Sangavi Sivagnanasundram reviewed gene: KAT6B: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005174; Phenotypes: KAT6B-related multiple congenital anomalies syndrome MONDO:0036042; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 KAT6A Sangavi Sivagnanasundram reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005173; Phenotypes: syndromic intellectual disability MONDO:0000508; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 IGBP1 Sangavi Sivagnanasundram reviewed gene: IGBP1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005117; Phenotypes: corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome MONDO:0010333; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 IDS Sangavi Sivagnanasundram reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005112; Phenotypes: mucopolysaccharidosis type 2 MONDO:0010674; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 HPRT1 Sangavi Sivagnanasundram reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005082; Phenotypes: Lesch-Nyhan syndrome MONDO:0010298; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 HOXA1 Sangavi Sivagnanasundram reviewed gene: HOXA1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005077; Phenotypes: syndromic intellectual disability MONDO:0000508; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5821 HNRNPK Sangavi Sivagnanasundram reviewed gene: HNRNPK: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005073; Phenotypes: neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome (Au-Kline syndrome) MONDO:0018681; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5821 HIST1H1E Sangavi Sivagnanasundram commented on gene: HIST1H1E
Intellectual disability syndromic and non-syndromic v0.5821 GPC3 Sangavi Sivagnanasundram reviewed gene: GPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004990; Phenotypes: Simpson-Golabi-Behmel syndrome MONDO:0010731; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 GDI1 Sangavi Sivagnanasundram reviewed gene: GDI1: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004941; Phenotypes: non-syndromic X-linked intellectual disability MONDO:0019181; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5821 FTSJ1 Sangavi Sivagnanasundram reviewed gene: FTSJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004892; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 FMR1 Sangavi Sivagnanasundram reviewed gene: FMR1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004870; Phenotypes: fragile X syndrome MONDO:0010383; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5821 SPR Zornitza Stark Marked gene: SPR as ready
Intellectual disability syndromic and non-syndromic v0.5821 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5821 SPR Zornitza Stark Phenotypes for gene: SPR were changed from to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716
Intellectual disability syndromic and non-syndromic v0.5820 SPR Zornitza Stark Publications for gene: SPR were set to
Intellectual disability syndromic and non-syndromic v0.5819 SPR Zornitza Stark Mode of inheritance for gene: SPR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5818 SPR Zornitza Stark reviewed gene: SPR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5818 MAST3 Zornitza Stark Publications for gene: MAST3 were set to 34185323
Intellectual disability syndromic and non-syndromic v0.5817 AGTR2 Zornitza Stark Phenotypes for gene: AGTR2 were changed from to X-linked complex neurodevelopmental disorder MONDO:0100148
Intellectual disability syndromic and non-syndromic v0.5816 AGTR2 Zornitza Stark Mode of inheritance for gene: AGTR2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5815 AGTR2 Zornitza Stark Tag disputed tag was added to gene: AGTR2.
Intellectual disability syndromic and non-syndromic v0.5815 AVPR1A Zornitza Stark Tag disputed tag was added to gene: AVPR1A.
Intellectual disability syndromic and non-syndromic v0.5815 BAZ2B Zornitza Stark Classified gene: BAZ2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5815 BAZ2B Zornitza Stark Gene: baz2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5814 BCORL1 Zornitza Stark Classified gene: BCORL1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5814 BCORL1 Zornitza Stark Gene: bcorl1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5813 CASK Zornitza Stark Publications for gene: CASK were set to
Intellectual disability syndromic and non-syndromic v0.5812 CASK Zornitza Stark Marked gene: CASK as ready
Intellectual disability syndromic and non-syndromic v0.5812 CASK Zornitza Stark Added comment: Comment when marking as ready: Microcephaly with pontine and cerebellar hypoplasia (MICPCH), generally associated with pathogenic loss-of-function variants in CASK
X-linked intellectual disability (XLID) with or without nystagmus, generally associated with hypomorphic CASK pathogenic variants
Intellectual disability syndromic and non-syndromic v0.5812 CASK Zornitza Stark Gene: cask has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5812 CASK Zornitza Stark Phenotypes for gene: CASK were changed from to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Intellectual disability, with or without nystagmus MIM#300422
Intellectual disability syndromic and non-syndromic v0.5811 CASK Zornitza Stark Mode of inheritance for gene: CASK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5810 CLIC2 Zornitza Stark Phenotypes for gene: CLIC2 were changed from Mental retardation, X-linked, syndromic 32, 300886 to Intellectual disability, X-linked, syndromic 32, 300886
Intellectual disability syndromic and non-syndromic v0.5809 CLIC2 Zornitza Stark Tag disputed tag was added to gene: CLIC2.
Intellectual disability syndromic and non-syndromic v0.5809 CNTN6 Zornitza Stark Tag disputed tag was added to gene: CNTN6.
Intellectual disability syndromic and non-syndromic v0.5809 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Intellectual disability syndromic and non-syndromic v0.5809 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5809 DHCR7 Zornitza Stark Publications for gene: DHCR7 were set to
Intellectual disability syndromic and non-syndromic v0.5808 DHCR7 Zornitza Stark Phenotypes for gene: DHCR7 were changed from to Smith-Lemli-Opitz syndrome MONDO:0010035
Intellectual disability syndromic and non-syndromic v0.5807 DHCR7 Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5806 DKC1 Zornitza Stark Marked gene: DKC1 as ready
Intellectual disability syndromic and non-syndromic v0.5806 DKC1 Zornitza Stark Gene: dkc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5806 DKC1 Zornitza Stark Publications for gene: DKC1 were set to
Intellectual disability syndromic and non-syndromic v0.5805 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from to DKC1-related disorder MONDO:0100152
Intellectual disability syndromic and non-syndromic v0.5804 DKC1 Zornitza Stark Mode of inheritance for gene: DKC1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5803 DPP6 Zornitza Stark Phenotypes for gene: DPP6 were changed from Mental retardation, autosomal dominant 33 (MIM#616311) to Intellectual disability, autosomal dominant 33 (MIM#616311)
Intellectual disability syndromic and non-syndromic v0.5802 DPP6 Zornitza Stark Classified gene: DPP6 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5802 DPP6 Zornitza Stark Gene: dpp6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5801 DPP6 Zornitza Stark Tag disputed tag was added to gene: DPP6.
Intellectual disability syndromic and non-syndromic v0.5801 FBN1 Zornitza Stark Tag disputed tag was added to gene: FBN1.
Intellectual disability syndromic and non-syndromic v0.5801 FLNA Zornitza Stark Marked gene: FLNA as ready
Intellectual disability syndromic and non-syndromic v0.5801 FLNA Zornitza Stark Gene: flna has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5801 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from to Heterotopia, periventricular, 1, MIM# 300049
Intellectual disability syndromic and non-syndromic v0.5800 FLNA Zornitza Stark Publications for gene: FLNA were set to
Intellectual disability syndromic and non-syndromic v0.5799 FLNA Zornitza Stark Mode of inheritance for gene: FLNA was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5798 FLNA Sangavi Sivagnanasundram reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004863; Phenotypes: periventricular nodular heterotopia MONDO:0020341; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5798 FBN1 Sangavi Sivagnanasundram reviewed gene: FBN1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004823; Phenotypes: Shprintzen-Goldberg syndrome MONDO:0008426; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 DPP6 Sangavi Sivagnanasundram reviewed gene: DPP6: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004701; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 DKC1 Sangavi Sivagnanasundram reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004651; Phenotypes: DKC1-related disorder MONDO:0100152; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5798 DHCR7 Sangavi Sivagnanasundram reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004643; Phenotypes: Smith-Lemli-Opitz syndrome MONDO:0010035; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5798 CNTN6 Sangavi Sivagnanasundram reviewed gene: CNTN6: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004489; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 CLIC2 Sangavi Sivagnanasundram reviewed gene: CLIC2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004469; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5798 CDH15 Sangavi Sivagnanasundram reviewed gene: CDH15: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004393; Phenotypes: intellectual disability MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 CASK Sangavi Sivagnanasundram reviewed gene: CASK: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004345; Phenotypes: X-linked syndromic intellectual disability MONDO:0020119; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5798 BCORL1 Sangavi Sivagnanasundram reviewed gene: BCORL1: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004254; Phenotypes: Shukla-Vernon syndrome MONDO:0026727; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5798 BAZ2B Sangavi Sivagnanasundram reviewed gene: BAZ2B: Rating: AMBER; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004237; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5798 AVPR1A Sangavi Sivagnanasundram reviewed gene: AVPR1A: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004223; Phenotypes: autism spectrum disorder MONDO:0005258; Mode of inheritance: Unknown
Intellectual disability syndromic and non-syndromic v0.5798 KDM5A Zornitza Stark Phenotypes for gene: KDM5A were changed from Neurodevelopmental disorder MONDO:0700092, KDM5A-related to Neurodevelopmental disorder MONDO:0700092, KDM5A-related; El Hayek-Chahrour neurodevelopmental syndrome, MIM# 620820
Intellectual disability syndromic and non-syndromic v0.5797 KDM5A Zornitza Stark edited their review of gene: KDM5A: Changed phenotypes: Neurodevelopmental disorder MONDO:0700092, KDM5A-related, El Hayek-Chahrour neurodevelopmental syndrome, MIM# 620820
Intellectual disability syndromic and non-syndromic v0.5797 ANKRD11 Sangavi Sivagnanasundram reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 25413698, https://search.clinicalgenome.org/CCID:004133; Phenotypes: KBG syndrome MONDO:0007846; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5797 AGTR2 Sangavi Sivagnanasundram reviewed gene: AGTR2: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:004075; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5797 MAST3 Sarah Leigh reviewed gene: MAST3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35095415; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5797 SPR Amy Chiang edited their review of gene: SPR: Added comment: SPR has been classified to have definitive association with dopa-responsive dystonia (reviewed by the Aminoacidopathy Expert Panel on 06/04/2021).

Clinical phenotypes are mainly neuromuscular with characteristic features of axial hypotonia, dystonia, delayed psychomotor development, oculogyric crises, diurnal fluctuation with improvement after sleep; though cognitive impairment ranging from mild to severe levels have been reported in patients with sepiapterin reductase deficiency (PMID: 16049044, 17188538) - 7 Maltese patients with the same homozygous spice variants in SPR (founder effect due to relative small Maltese population); note there was no significant improvement in cognitive ability with L-dopa treatment in these patients despite improvement in their motor abilities (PMID: 16049044) - ? other causes to cognitive impairment in these patients other than SPR associated sepiapterin reductase deficiency

There are 271 SPR variants registered in ClinVar to date with only 1 submission from a research lab reported 2 affected individuals with intellectual disability + family history (ClinVar # 625209) - no publication available to verify, ? from BRIDGE consortium study: SPEED project cohort
A start loss variant detected in 5 affected individuals with ID & epilepsy from a Persian consanguineous family - LOD score = 4.027 (PMID: 29302074); Changed publications: PMID: 29302074, 16049044, 17188538; Changed phenotypes: MONDO #0012994, OMIM #612716, axial hypotonia, dystonia with diurnal fluctuation, oculogyric crises, delayed psychomotor development, sepiapterin reductase deficiency
Intellectual disability syndromic and non-syndromic v0.5797 COG4 Zornitza Stark Marked gene: COG4 as ready
Intellectual disability syndromic and non-syndromic v0.5797 COG4 Zornitza Stark Gene: cog4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5797 COG4 Zornitza Stark Phenotypes for gene: COG4 were changed from to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489
Intellectual disability syndromic and non-syndromic v0.5796 SPR Amy Chiang changed review comment from: SPR has been classified to have definitive association with dopa-responsive dystonia. This was reviewed by the Aminoacidopathy Expert Panel on 06/04/2021.
There are 271 SPR variants registered in ClinVar to date with only 1 submission from a research lab reported 2 affected individuals with intellectual disability + family history (ClinVar # 625209) - no publication available to verify, ? from BRIDGE consortium study: SPEED project cohort
A start loss variant detected in 5 affected individuals with ID & epilepsy from a Persian consanguineous family - LOD score = 4.027 (PMID: 29302074); to: SPR has been classified to have definitive association with dopa-responsive dystonia. This was reviewed by the Aminoacidopathy Expert Panel on 06/04/2021.
There are 271 SPR variants registered in ClinVar to date with only 1 submission from a research lab reported 2 affected individuals with intellectual disability + family history (ClinVar # 625209) - no publication available to verify, ? from BRIDGE consortium study: SPEED project cohort
A start loss variant detected in 5 affected individuals with ID & epilepsy from a Persian consanguineous family - LOD score = 4.027 (PMID: 29302074)
Intellectual disability syndromic and non-syndromic v0.5796 SPR Amy Chiang reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29302074; Phenotypes: dopa-responsive dystonia due to sepiapterin reductase deficiency, MONDO: 0012994, Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM: 612716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5796 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015 to Glutamine deficiency, congenital MIM#610015; Developmental and epileptic encephalopathy 116, MIM# 620806
Intellectual disability syndromic and non-syndromic v0.5795 GLUL Zornitza Stark edited their review of gene: GLUL: Changed phenotypes: Glutamine deficiency, congenital MIM#610015, Developmental and epileptic encephalopathy 116, MIM# 620806
Intellectual disability syndromic and non-syndromic v0.5795 DAGLA Zornitza Stark Marked gene: DAGLA as ready
Intellectual disability syndromic and non-syndromic v0.5795 DAGLA Zornitza Stark Gene: dagla has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5795 DAGLA Zornitza Stark Classified gene: DAGLA as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5795 DAGLA Zornitza Stark Gene: dagla has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5794 DAGLA Zornitza Stark gene: DAGLA was added
gene: DAGLA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to 35737950
Phenotypes for gene: DAGLA were set to Neuroocular syndrome 2, paroxysmal type, MIM# 168885
Review for gene: DAGLA was set to GREEN
Added comment: 9 individuals from 8 families reported with daily paroxysmal spells characterized by eye deviation or nystagmus with abnormal head posturing apparent from birth or early infancy. The episodes tend to be triggered after sleeping, and most patients show improvement of the ocular symptoms over time. Affected individuals also have hypotonia, mild developmental delay, dysarthria, and gait ataxia; most have mildly impaired intellectual development. Seizures are not observed.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Zornitza Stark Tag new gene name tag was added to gene: CYHR1.
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Bryony Thompson Classified gene: CYHR1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5793 CYHR1 Bryony Thompson Gene: cyhr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5792 CYHR1 Bryony Thompson reviewed gene: CYHR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38641995; Phenotypes: neurodevelopmental disorder MONDO:0700092, ZTRAF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5792 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM#125310
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Classified gene: NOTCH3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5791 NOTCH3 Ain Roesley Gene: notch3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5790 NOTCH3 Ain Roesley changed review comment from: Pre-print (https://sciprofiles.com/publication/view/62eb776390415f0166f73fae7cd172ed)

Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism

AR missense are associated with CADASIL-like phenotype; to: Pre-print (https://sciprofiles.com/publication/view/62eb776390415f0166f73fae7cd172ed)

Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism; seizures, spasticity, hypotonia, ataxia

AR missense are associated with CADASIL-like phenotype
Intellectual disability syndromic and non-syndromic v0.5790 NOTCH3 Ain Roesley reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Marked gene: SLC35C1 as ready
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5790 SLC35C1 Zornitza Stark Phenotypes for gene: SLC35C1 were changed from to Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953
Intellectual disability syndromic and non-syndromic v0.5789 SLC35C1 Zornitza Stark Publications for gene: SLC35C1 were set to
Intellectual disability syndromic and non-syndromic v0.5788 SLC35C1 Zornitza Stark Mode of inheritance for gene: SLC35C1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Marked gene: PRMT9 as ready
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Gene: prmt9 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5787 PRMT9 Zornitza Stark Phenotypes for gene: PRMT9 were changed from Neurodevelopmental disorder, MONDO:0100500 to Neurodevelopmental disorder, MONDO:0100500, PRMT9-related
Intellectual disability syndromic and non-syndromic v0.5786 PRMT9 Chirag Patel gene: PRMT9 was added
gene: PRMT9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRMT9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRMT9 were set to PMID: 38561334
Phenotypes for gene: PRMT9 were set to Neurodevelopmental disorder, MONDO:0100500
Review for gene: PRMT9 was set to RED
Added comment: A homozygous variant (G189R) in PRMT9 is reported based on large WGS study in 136 consanguineous families - unclear if only found in 1 family and no clinical information on case(s).

PMRTs (protein arginine methyltransferases) catalyse post translational modification via arginine methylation. Functional studies showed that the G189R variant abolishes PRMT9's methyltransferase activity - specifically at the R508 residue of SF3B2 RNA (exclusively methylated by PRMT9) - and leads to heavy PRMT9 ubiquitination, and abnormal splicing activity of SF3B2. Knock out mouse model showed PRMT9 loss in excitatory neurons leads to aberrant synapse development and impaired learning and memory.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5785 OTUD7A Zornitza Stark Phenotypes for gene: OTUD7A were changed from Intellectual disability; Epilepsy to Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Intellectual disability syndromic and non-syndromic v0.5784 OTUD7A Zornitza Stark edited their review of gene: OTUD7A: Changed phenotypes: Neurodevelopmental disorder with hypotonia and seizures, MIM# 620790
Intellectual disability syndromic and non-syndromic v0.5784 SLC35C1 Yixin JIANG reviewed gene: SLC35C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33836758, 32313197, 34389986; Phenotypes: Congenital disorder of glycosylation, type IIc, MIM# 266265, MONDO:0009953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5784 PTRH2 Bryony Thompson Publications for gene: PTRH2 were set to 25574476; 28175314; 28328138; 25558065; 27129381
Intellectual disability syndromic and non-syndromic v0.5783 PTRH2 Bryony Thompson Classified gene: PTRH2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5783 PTRH2 Bryony Thompson Gene: ptrh2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5782 PTRH2 Bryony Thompson reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33092935, 37239392; Phenotypes: neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 MONDO:8000012; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5782 DMAP1 Ben Lundie reviewed gene: DMAP1: Rating: AMBER; Mode of pathogenicity: Other; Publications: ; Phenotypes: Unknown.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5782 SLC1A1 Bryony Thompson Classified gene: SLC1A1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5782 SLC1A1 Bryony Thompson Gene: slc1a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5781 RNU4-2 Zornitza Stark changed review comment from: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature; to: Over 100 individuals with ID found to have de novo variants in this gene. Please note difficult to identify on ES.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5781 RNU4-2 Zornitza Stark Publications for gene: RNU4-2 were set to
Intellectual disability syndromic and non-syndromic v0.5780 RNU4-2 Zornitza Stark edited their review of gene: RNU4-2: Changed publications: 38645094
Intellectual disability syndromic and non-syndromic v0.5780 MAB21L1 Zornitza Stark reviewed gene: MAB21L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar, ocular, craniofacial, and genital syndrome MIM#618479; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5780 FOSL2 Zornitza Stark Phenotypes for gene: FOSL2 were changed from Neurodevelopmental disorder, MONDO:0700092, FOSL2-related to Aplasia cutis-enamel dysplasia syndrome, MIM# 620789
Intellectual disability syndromic and non-syndromic v0.5779 FOSL2 Zornitza Stark reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM# 620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5779 ACBD6 Zornitza Stark Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder (MONDO#0700092), ACBD6-related to Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785
Intellectual disability syndromic and non-syndromic v0.5778 ACBD6 Zornitza Stark reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM# 620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5778 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Intellectual disability syndromic and non-syndromic v0.5778 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Intellectual disability syndromic and non-syndromic v0.5777 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Intellectual disability syndromic and non-syndromic v0.5777 SOX2 Zornitza Stark Gene: sox2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Marked gene: STRA6 as ready
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Gene: stra6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5777 STRA6 Zornitza Stark Phenotypes for gene: STRA6 were changed from to Matthew-Wood syndrome MONDO:0011010
Intellectual disability syndromic and non-syndromic v0.5776 STRA6 Zornitza Stark Publications for gene: STRA6 were set to
Intellectual disability syndromic and non-syndromic v0.5775 STRA6 Zornitza Stark Mode of inheritance for gene: STRA6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5774 UFC1 Zornitza Stark Marked gene: UFC1 as ready
Intellectual disability syndromic and non-syndromic v0.5774 UFC1 Zornitza Stark Gene: ufc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Intellectual disability syndromic and non-syndromic v0.5774 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Marked gene: WDPCP as ready
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Gene: wdpcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5774 WDPCP Zornitza Stark Phenotypes for gene: WDPCP were changed from to Bardet-Biedl syndrome 15, MIM# 615992; OFD; Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085
Intellectual disability syndromic and non-syndromic v0.5773 ZIC1 Zornitza Stark Marked gene: ZIC1 as ready
Intellectual disability syndromic and non-syndromic v0.5773 ZIC1 Zornitza Stark Gene: zic1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5773 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Developmental and epileptic encephalopathy 115, MIM#620783 to Developmental and epileptic encephalopathy 115, MIM#620783; Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Intellectual disability syndromic and non-syndromic v0.5772 SNF8 Zornitza Stark commented on gene: SNF8: Four individuals from 3 families with NDD plus OA, rather than DEE.
Intellectual disability syndromic and non-syndromic v0.5772 SNF8 Zornitza Stark edited their review of gene: SNF8: Changed phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783, Neurodevelopmental disorder plus optic atrophy, MIM# 620784
Intellectual disability syndromic and non-syndromic v0.5772 NSUN6 Zornitza Stark Phenotypes for gene: NSUN6 were changed from neurodevelopmental disorder MONDO:0700092, NSUN6-related to Intellectual developmental disorder, autosomal recessive 82, MIM# 620779
Intellectual disability syndromic and non-syndromic v0.5771 NSUN6 Zornitza Stark reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 82, MIM# 620779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5771 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder, MIM# 620782; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Intellectual disability syndromic and non-syndromic v0.5770 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Intellectual disability syndromic and non-syndromic v0.5769 SNF8 Zornitza Stark Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Developmental and epileptic encephalopathy 115, MIM#620783
Intellectual disability syndromic and non-syndromic v0.5768 SNF8 Zornitza Stark reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5768 PURA Ain Roesley Phenotypes for gene: PURA were changed from Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158) to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Intellectual disability syndromic and non-syndromic v0.5768 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark Marked gene: BANF1 as ready
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark Gene: banf1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5767 BANF1 Zornitza Stark gene: BANF1 was added
gene: BANF1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BANF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BANF1 were set to 35982159
Phenotypes for gene: BANF1 were set to Neurodevelopmental disorder, MONDO:0700092, BANF1-related
Review for gene: BANF1 was set to RED
Added comment: Single individual reported with a de novo variant, p.Ala87Thr, and a neurodevelopmental disorder.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Marked gene: RNU4-2 as ready
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Classified gene: RNU4-2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5766 RNU4-2 Zornitza Stark Gene: rnu4-2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5765 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Emerging evidence that de novo variants in this gene cause ID.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Marked gene: YKT6 as ready
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Classified gene: YKT6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5764 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5763 YKT6 Zornitza Stark gene: YKT6 was added
gene: YKT6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YKT6 were set to 38522068
Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related
Review for gene: YKT6 was set to AMBER
Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila. Amber rating due to homozygous missense variants and founder effect in two of the families.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Marked gene: SEPHS1 as ready
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Classified gene: SEPHS1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5762 SEPHS1 Zornitza Stark Gene: sephs1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5761 SEPHS1 Zornitza Stark gene: SEPHS1 was added
gene: SEPHS1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092, SEPHS1-related
Review for gene: SEPHS1 was set to GREEN
Added comment: Nine individuals from eight families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight of these individuals had a recurrent variant at amino acid position 371 of SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were known to be de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Marked gene: GLUL as ready
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Gene: glul has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5760 GLUL Zornitza Stark Phenotypes for gene: GLUL were changed from to Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related; Glutamine deficiency, congenital MIM#610015
Intellectual disability syndromic and non-syndromic v0.5759 GLUL Zornitza Stark Publications for gene: GLUL were set to
Intellectual disability syndromic and non-syndromic v0.5758 GLUL Zornitza Stark Mode of inheritance for gene: GLUL was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5757 GLUL Zornitza Stark reviewed gene: GLUL: Rating: GREEN; Mode of pathogenicity: None; Publications: 16267323, 21353613, 33150193; Phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062, GLUL-related, Glutamine deficiency, congenital MIM#610015, disorder of amino acid metabolism; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Marked gene: GTF3C5 as ready
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Classified gene: GTF3C5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5757 GTF3C5 Bryony Thompson Gene: gtf3c5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5756 GTF3C5 Bryony Thompson gene: GTF3C5 was added
gene: GTF3C5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
gene: GTF3C5 was marked as current diagnostic
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5755 CEP295 Zornitza Stark Marked gene: CEP295 as ready
Intellectual disability syndromic and non-syndromic v0.5755 CEP295 Zornitza Stark Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5755 PLXNB2 Zornitza Stark Phenotypes for gene: PLXNB2 were changed from Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related to Syndromic disease MONDO:0002254, PLXNB2 -related
Intellectual disability syndromic and non-syndromic v0.5754 PLXNB2 Zornitza Stark Marked gene: PLXNB2 as ready
Intellectual disability syndromic and non-syndromic v0.5754 PLXNB2 Zornitza Stark Gene: plxnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5754 DISP1 Zornitza Stark Phenotypes for gene: DISP1 were changed from Holoprosencephaly, MONDO:0016296 to Holoprosencephaly (MONDO:0016296), DISP1-related
Intellectual disability syndromic and non-syndromic v0.5753 DISP1 Zornitza Stark Publications for gene: DISP1 were set to 19184110; 26748417; 23542665
Intellectual disability syndromic and non-syndromic v0.5752 DISP1 Zornitza Stark Mode of inheritance for gene: DISP1 was changed from Other to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5751 DISP1 Zornitza Stark Classified gene: DISP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5751 DISP1 Zornitza Stark Gene: disp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5750 DISP1 Zornitza Stark edited their review of gene: DISP1: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.5750 DISP1 Zornitza Stark edited their review of gene: DISP1: Added comment: PMID: 38529886
25 individuals from 20 unrelated families with a phenotype associated with mild holoprosencephaly (HPE).
A total of 23 different variants were identified in DISP1 (missense, frameshift and nonsense).
14 heterozygous individuals , 5 compound heterozygous individuals, 6 homozygous individuals (5 of the individuals were from 3 unrelated consanguineous families).

HPE phenotype was also seen prenatally as one of the reported monoallelic individuals was a fetus at 20+6 GW prior to passing due to MTP.; Changed publications: 19184110, 26748417, 23542665, 38529886; Changed phenotypes: Holoprosencephaly (MONDO:0016296), DISP1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5750 DOCK4 Bryony Thompson Phenotypes for gene: DOCK4 were changed from to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Intellectual disability syndromic and non-syndromic v0.5749 DOCK4 Bryony Thompson Publications for gene: DOCK4 were set to
Intellectual disability syndromic and non-syndromic v0.5748 DOCK4 Bryony Thompson Mode of inheritance for gene: DOCK4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5747 DOCK4 Bryony Thompson Classified gene: DOCK4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5747 DOCK4 Bryony Thompson Gene: dock4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5746 DOCK4 Sangavi Sivagnanasundram changed review comment from: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).; to: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Intellectual disability syndromic and non-syndromic v0.5746 DOCK4 Sangavi Sivagnanasundram changed review comment from: Well-established gene-disease association

7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).; to: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Marked gene: FRYL as ready
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Classified gene: FRYL as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5746 FRYL Ain Roesley Gene: fryl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5745 FRYL Ain Roesley gene: FRYL was added
gene: FRYL was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to neurodevelopmental disorder MONDO:0700092, FRYL-related
Review for gene: FRYL was set to GREEN
gene: FRYL was marked as current diagnostic
Added comment: 14 individuals, all de novo except 1x duo testing (not present in tested father)
5x missense + 8x fs/stopgain + 1x canonical splice

13/13 with ID/DD (1x deceased)
4/14 seizures
7/14 with cardiac anomalies such as PDA, TOF, VSD, dextrocardia

1x also has a de novo fs variant in SF3B4
1x also has a de novo stop gain variant in SDHA

functional studies using flies were performed
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Marked gene: KCNB2 as ready
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Classified gene: KCNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5744 KCNB2 Ain Roesley Gene: kcnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5743 KCNB2 Ain Roesley gene: KCNB2 was added
gene: KCNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
gene: KCNB2 was marked as current diagnostic
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5742 DOCK4 Sangavi Sivagnanasundram edited their review of gene: DOCK4: Changed rating: GREEN
Intellectual disability syndromic and non-syndromic v0.5742 PLXNB2 Chirag Patel Classified gene: PLXNB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5742 PLXNB2 Chirag Patel Gene: plxnb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5741 PLXNB2 Chirag Patel gene: PLXNB2 was added
gene: PLXNB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to PMID: 38458752
Phenotypes for gene: PLXNB2 were set to Amelogenesis imperfecta MONDO:0019507, PLXNB2 -related; Sensorineural hearing loss disorder MONDO:0020678, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
gene: PLXNB2 was marked as current diagnostic
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5740 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Classified gene: CEP295 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5739 CEP295 Chirag Patel Gene: cep295 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5738 CEP295 Chirag Patel gene: CEP295 was added
gene: CEP295 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to PMID: 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Review for gene: CEP295 was set to GREEN
gene: CEP295 was marked as current diagnostic
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5737 USP27X Zornitza Stark Phenotypes for gene: USP27X were changed from Mental retardation, X-linked 105, MIM#300984 to Intellectual disability, X-linked 105, MIM#300984
Intellectual disability syndromic and non-syndromic v0.5736 USP27X Zornitza Stark Publications for gene: USP27X were set to 25644381
Intellectual disability syndromic and non-syndromic v0.5735 USP27X Zornitza Stark Classified gene: USP27X as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5735 USP27X Zornitza Stark Gene: usp27x has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5734 USP27X Zornitza Stark edited their review of gene: USP27X: Added comment: Ten additional individuals and further experimental data reported.; Changed rating: GREEN; Changed publications: 25644381, 38182161; Changed phenotypes: Intellectual disability, X-linked 105, MIM#300984
Intellectual disability syndromic and non-syndromic v0.5734 FEM1B Zornitza Stark Phenotypes for gene: FEM1B were changed from Syndromic intellectual disability to Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5733 FEM1B Zornitza Stark Publications for gene: FEM1B were set to 31036916
Intellectual disability syndromic and non-syndromic v0.5732 FEM1B Zornitza Stark Classified gene: FEM1B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5732 FEM1B Zornitza Stark Gene: fem1b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5731 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications: 31036916, 38465576; Changed phenotypes: Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Marked gene: USP14 as ready
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Classified gene: USP14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5731 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5730 USP14 Zornitza Stark Classified gene: USP14 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5730 USP14 Zornitza Stark Gene: usp14 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5729 USP14 Zornitza Stark gene: USP14 was added
gene: USP14 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: USP14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP14 were set to 38469793; 35066879
Phenotypes for gene: USP14 were set to Syndromic disease MONDO:0002254, USP14-related
Review for gene: USP14 was set to AMBER
Added comment: AMBER rating as two of the families had affected fetuses, one had a severely affected newborn, and fourth had a progressive course: none fit well with ID, though there's likely to be a continuum.

PMID 35066879: 3 fetuses from 2 different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11) in USP14, and sequencing of family members showed segregation with the phenotype. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human multiple congenital contractures phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay.

PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5728 DOCK4 Sangavi Sivagnanasundram reviewed gene: DOCK4: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38526744; Phenotypes: DOCK4-related neurodevelopmental disorder (MONDO:0060490); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5728 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from Neurodevelopmental disorder, MONDO:0700092, ZFX-related to Intellectual developmental disorder, X-linked syndromic 37, MIM# 301118
Intellectual disability syndromic and non-syndromic v0.5727 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755 to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755; Developmental and epileptic encephalopathy 114, MIM# 620774
Intellectual disability syndromic and non-syndromic v0.5726 SLC32A1 Zornitza Stark reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 114, MIM# 620774; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5726 CRELD1 Zornitza Stark Phenotypes for gene: CRELD1 were changed from Neurodevelopmental disorder (MONDO:0700092), CRELD1-related to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Intellectual disability syndromic and non-syndromic v0.5725 CRELD1 Zornitza Stark reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5725 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Neurodevelopmental disorder, MONDO:0700092, SV2A-related to Neurodevelopmental disorder, MONDO:0700092, SV2A-related; Developmental and epileptic encephalopathy 113, MIM# 620772
Intellectual disability syndromic and non-syndromic v0.5724 SV2A Zornitza Stark reviewed gene: SV2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 113, MIM# 620772; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5724 ZFHX3 Zornitza Stark Publications for gene: ZFHX3 were set to 37292950
Intellectual disability syndromic and non-syndromic v0.5723 ZFHX3 Zornitza Stark edited their review of gene: ZFHX3: Added comment: Now published PMID 38412861; Changed publications: 38412861
Intellectual disability syndromic and non-syndromic v0.5723 SLC32A1 Zornitza Stark Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy MONDO:0100062, SLC32A1-related to Generalized epilepsy with febrile seizures plus, type 12, MIM# 620755
Intellectual disability syndromic and non-syndromic v0.5722 PTRHD1 Zornitza Stark Phenotypes for gene: PTRHD1 were changed from Parkinsonism; Intellectual disability to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Intellectual disability syndromic and non-syndromic v0.5721 PTRHD1 Zornitza Stark edited their review of gene: PTRHD1: Changed phenotypes: Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, MIM# 620747
Intellectual disability syndromic and non-syndromic v0.5721 SLC4A10 Zornitza Stark Phenotypes for gene: SLC4A10 were changed from Neurodevelopmental disorderMONDO:0700092, SLC4A10-related to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746
Intellectual disability syndromic and non-syndromic v0.5720 SLC4A10 Zornitza Stark reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM# 620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Marked gene: ZSCAN10 as ready
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Classified gene: ZSCAN10 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5720 ZSCAN10 Zornitza Stark Gene: zscan10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Marked gene: CELSR3 as ready
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Classified gene: CELSR3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5719 CELSR3 Zornitza Stark Gene: celsr3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5718 NARS Zornitza Stark changed review comment from: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).; to: Both MOIs assessed as MODERATE by ClinGen.
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Marked gene: SLC12A9 as ready
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5718 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 CELSR3 Crystle Lee gene: CELSR3 was added
gene: CELSR3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to PMID: 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder (MONDO#0700092), CELSR3-related
Review for gene: CELSR3 was set to GREEN
Added comment: PMID: 38429302:12 affected individuals from 11 families reported with bi-allelic variants. Phenotype ranged from CNS anomalies (7/12), CNS and CAKUT (3/12) and CAKUT only (2/12). 8/12 has ID/DD. Only missense variants reported and 1 inframe variant. Functional studies done in zebrafish demonstrate similar structural anomalies of the developing pronephros and neuronal abnormalities to affected individuals
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Marked gene: DIP2C as ready
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5717 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Classified gene: DIP2C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5717 DIP2C Elena Savva Gene: dip2c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5716 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Classified gene: SLC12A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5716 SLC12A9 Zornitza Stark Gene: slc12a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5715 ZSCAN10 Rylee Peters gene: ZSCAN10 was added
gene: ZSCAN10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to PMID: 38386308
Phenotypes for gene: ZSCAN10 were set to Syndromic disease MONDO:0002254
Review for gene: ZSCAN10 was set to GREEN
Added comment: Bi-allelic ZSCAN10 loss-of-function variants were identified in seven affected individuals from five unrelated families with syndromic neurodevelopmental disorder.

Highly consistent phenotypic features include global developmental delay, behavioural abnormalities, and variable facial asymmetry with outer and inner ear malformations leading to profound SNHL.

Facial asymmetry was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Neurodevelopmental disorder (MONDO:0700092), SNF8-related to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Intellectual disability syndromic and non-syndromic v0.5715 SNF8 Elena Savva Phenotypes for gene: SNF8 were changed from Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia to Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Intellectual disability syndromic and non-syndromic v0.5715 POP1 Ain Roesley Publications for gene: POP1 were set to
Intellectual disability syndromic and non-syndromic v0.5714 SLC12A9 Zornitza Stark gene: SLC12A9 was added
gene: SLC12A9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC12A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A9 were set to 38334070
Phenotypes for gene: SLC12A9 were set to Neurodevelopmental disorder, MONDO:0700092, SLC12A9-related
Review for gene: SLC12A9 was set to GREEN
Added comment: Three individuals from unrelated families with bi-allelic LoF variants and a neurodevelopmental phenotype, skeletal abnormalities, brain abnormalities, hypopigmentation, dysmorphic features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Marked gene: SNF8 as ready
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Classified gene: SNF8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5714 SNF8 Elena Savva Gene: snf8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5713 SNF8 Chern Lim edited their review of gene: SNF8: Changed phenotypes: Neurodevelopmental disorder (MONDO:0700092), SNF8-related
Intellectual disability syndromic and non-syndromic v0.5713 DIP2C Melanie Marty gene: DIP2C was added
gene: DIP2C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to PMID: 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO#0700092), DIP2C-related
Review for gene: DIP2C was set to GREEN
Added comment: PMID: 38421105 - Twenty three patients with het DIP2C variants (10 de novo).
All patients had developmental delays affecting expressive language and speech, most had mild dev delay and ID. Four patients had seizures. Additional phenotypic findings were non-specific but recurrent anomalies did include a high anterior hair-line, prominent forehead, and a broad nasal tip. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects,and bicuspid aortic valve)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5713 DENND5B Elena Savva Publications for gene: DENND5B were set to
Intellectual disability syndromic and non-syndromic v0.5713 DENND5B Elena Savva Mode of pathogenicity for gene: DENND5B was changed from None to None
Intellectual disability syndromic and non-syndromic v0.5712 SNF8 Chern Lim gene: SNF8 was added
gene: SNF8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia
Review for gene: SNF8 was set to GREEN
gene: SNF8 was marked as current diagnostic
Added comment: PMID: 38423010
- Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified.
- The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.
- Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Marked gene: RREB1 as ready
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Classified gene: RREB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5712 RREB1 Zornitza Stark Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5711 POP1 Belinda Chong reviewed gene: POP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38351533; Phenotypes: Anauxetic dysplasia 2, MIM#617396; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5711 RREB1 Zornitza Stark gene: RREB1 was added
gene: RREB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to 32938917; 38332451
Phenotypes for gene: RREB1 were set to Rasopathy, MONDO:0021060, RREB1-related
Review for gene: RREB1 was set to AMBER
Added comment: PMID 32938917: Single individual reported with Noonan syndrome-like features and a deletion encompassing RREB1. Overlapping deletions in publicly reported databases examined, and RREB1 postulated to be the key gene. Rreb1 hemizygous mice display orbital hypertelorism and age dependent cardiac hypertrophy. RREB1 recruits SIN3A and KDM1A to an RRE in target promoters in human and murine cells to control histone H3K4 methylation of MAPK pathway genes. In summary, single well phenotyped individual with a CNV and experimental data to support gene-disease association.

PMID 38332451: de novo LoF variant in an individual with phenotype consistent with the previous reports.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Marked gene: FEZF2 as ready
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Classified gene: FEZF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5710 FEZF2 Ain Roesley Gene: fezf2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5709 FEZF2 Ain Roesley gene: FEZF2 was added
gene: FEZF2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FEZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FEZF2 were set to 38425142
Phenotypes for gene: FEZF2 were set to neurodevelopmental disorder MONDO:0700092, FEZF2-related
Review for gene: FEZF2 was set to GREEN
gene: FEZF2 was marked as current diagnostic
Added comment: - 7 indiv but 1 has whole gene deletion and 6x SNV (4x PTCs and 2x same missense Arg344Cys)
- of the 6x SNV, 4x de novo + 1x from affected father
- all have ID/ASD
- 1x seizures
- 1x hypotonia
- 1x motor coordination disorder
- 2x enuresis after 7yo
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5708 ZFX Zornitza Stark Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Neurodevelopmental disorder, MONDO:0700092, ZFX-related
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Marked gene: ZFX as ready
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Classified gene: ZFX as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5707 ZFX Zornitza Stark Gene: zfx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5706 NARS Zornitza Stark commented on gene: NARS: AR disorder: assessed as LIMITED by ClinGen (borderline MODERATE).
Intellectual disability syndromic and non-syndromic v0.5706 ZFX Sarah Leigh gene: ZFX was added
gene: ZFX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZFX 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: ZFX were set to 26350204; 26740508; 38325380
Phenotypes for gene: ZFX were set to X-linked neurodevelopmental disorder with recurrent facial gestalt
Review for gene: ZFX was set to GREEN
Added comment: To date, germline variants in ZFX have not been associated with a phenotype in OMIM or Gen2Phen.
A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5706 PI4K2A Zornitza Stark Phenotypes for gene: PI4K2A were changed from complex neurodevelopmental disorder with motor features, PI4K2A-related, MONDO:0100516 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM# 620732
Intellectual disability syndromic and non-syndromic v0.5705 CBL Hali Van Niel reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20694012, 20543203, 11315197; Phenotypes: CBL-related disorder MONDO:0013308; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 CACNA1A Hali Van Niel reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27476654, 33985586; Phenotypes: developmental and epileptic encephalopathy, 42 MONDO:0014917; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 C12orf65 Hali Van Niel reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: None; Publications: 24284555, 20598281, 23188110, 24080142, PMID: 3479531; Phenotypes: hereditary spastic paraplegia 55 MONDO:0014020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BTD Hali Van Niel reviewed gene: BTD: Rating: GREEN; Mode of pathogenicity: None; Publications: 7550325, 9375914, 37751899, 32741581; Phenotypes: biotinidase deficiency MONDO:0009665; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BSCL2 Hali Van Niel reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12362029, 26072926, 28916377; Phenotypes: congenital generalized lipodystrophy type 2 MONDO:0010020; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCS1L Hali Van Niel reviewed gene: BCS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 9777342, 17314340, 11528392, 30582773, 30582773, 25914718; Phenotypes: Bjornstad syndrome MONDO:0009872; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCKDHB Hali Van Niel reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 7672509, 11509994, 14742428; Phenotypes: maple syrup urine disease type 1B MONDO:0023692; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BCKDHA Hali Van Niel reviewed gene: BCKDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 7883996, 7672509, 34288399; Phenotypes: maple syrup urine disease type 1A MONDO:0023691; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS2 Hali Van Niel reviewed gene: BBS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11285252, 11567139; Phenotypes: Bardet-Biedl syndrome 2 MONDO:0014432; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS12 Hali Van Niel reviewed gene: BBS12: Rating: GREEN; Mode of pathogenicity: None; Publications: 17160889, 20827784; Phenotypes: Bardet-Biedl syndrome 12 MONDO:0014440; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS10 Hali Van Niel reviewed gene: BBS10: Rating: GREEN; Mode of pathogenicity: None; Publications: 16582908, 20805367, 27245532; Phenotypes: Phenotype: Bardet-Biedl syndrome 10 MONDO:0014438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 BBS1 Hali Van Niel reviewed gene: BBS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12118255, 12677556, 12567324; Phenotypes: Bardet-Biedl syndrome 1 MONDO:0008854; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5705 WASHC4 Elena Savva Phenotypes for gene: WASHC4 were changed from ?Mental retardation, autosomal recessive 43; OMIM #615817 to Intellectual developmental disorder, autosomal recessive 43 MIM#615817
Intellectual disability syndromic and non-syndromic v0.5704 PUM1 Zornitza Stark Phenotypes for gene: PUM1 were changed from Spinocerebellar ataxia 47, MIM#617931; intellectual disability; epilepsy to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 PUM1 Zornitza Stark edited their review of gene: PUM1: Changed phenotypes: Spinocerebellar ataxia 47, MIM#617931, Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM# 620719
Intellectual disability syndromic and non-syndromic v0.5703 TRMT1 Elena Savva Phenotypes for gene: TRMT1 were changed from Mental retardation, autosomal recessive 68; OMIM #618302 to Intellectual developmental disorder, autosomal recessive 68 MIM#618302
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Marked gene: HMBS as ready
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5702 HMBS Zornitza Stark Publications for gene: HMBS were set to 15534187
Intellectual disability syndromic and non-syndromic v0.5701 HMBS Zornitza Stark Classified gene: HMBS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5701 HMBS Zornitza Stark Gene: hmbs has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5700 HMBS Zornitza Stark edited their review of gene: HMBS: Changed publications: 15534187, 34089223; Changed phenotypes: Encephalopathy, porphyria-related MIM#620704, Leukoencephalopathy, porphyria-related, MIM#620711
Intellectual disability syndromic and non-syndromic v0.5700 HMBS Zornitza Stark gene: HMBS was added
gene: HMBS was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: HMBS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMBS were set to 15534187
Phenotypes for gene: HMBS were set to Encephalopathy, porphyria-related MIM#620704; Leukoencephalopathy, porphyria-related, MIM#620711
Review for gene: HMBS was set to GREEN
Added comment: Several families reported with encephalopathy/leukoencephalopathy and ballelic variants in this gene.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni edited their review of gene: DDX3X: Changed publications: PMID: 32135084, 32852922
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni changed review comment from: Genotype-Phenotype Correlations

Females. Affected females with a subset of missense variants generally are more severely affected than those with truncating variants [Lennox et al 2020].

Polymicrogyria has been associated with missense or in-frame deletions [Lennox et al 2020].

Males. While all affected males have had missense DDX3X variants (see Table 6), their female relatives who are heterozygous for the same DDX3X variant do not manifest an atypical neurodevelopmental phenotype.; to: Genotype-Phenotype Correlations

Females. Affected females with a subset of missense variants generally are more severely affected than those with truncating variants PMID: 32135084

Polymicrogyria has been associated with missense or in-frame deletions PMID: 32135084

Males. While all affected males have had missense DDX3X variants , their female relatives who are heterozygous for the same DDX3X variant do not manifest an atypical neurodevelopmental phenotype.
Intellectual disability syndromic and non-syndromic v0.5699 DDX3X Abhijit Kulkarni commented on gene: DDX3X
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Classified gene: TMLHE as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Added comment: Comment on list classification: ClinGen Disputed gene-disease association Classification - 03/02/2021 by ID & Autism GCEP: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a780ea6-ad4e-417a-a596-27188e327aad-2021-03-02T050000.000Z?page=1&size=25&search=
Intellectual disability syndromic and non-syndromic v0.5699 TMLHE Bryony Thompson Gene: tmlhe has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5698 FBXO31 Lucy Spencer reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5698 TET3 Elena Savva Phenotypes for gene: TET3 were changed from Intellectual disability; dysmorphic features; abnormal growth; movement disorders to Beck-Fahrner syndrome MIM#618798
Intellectual disability syndromic and non-syndromic v0.5697 MAX Zornitza Stark Phenotypes for gene: MAX were changed from Syndromic disease (MONDO:0002254), MAX-related to Polydactyly-macrocephaly syndrome, MIM# 620712
Intellectual disability syndromic and non-syndromic v0.5696 TAF1C Zornitza Stark Marked gene: TAF1C as ready
Intellectual disability syndromic and non-syndromic v0.5696 TAF1C Zornitza Stark Gene: taf1c has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5696 NDUFB9 Zornitza Stark Publications for gene: NDUFB9 were set to 22200994
Intellectual disability syndromic and non-syndromic v0.5695 NDUFB9 Zornitza Stark edited their review of gene: NDUFB9: Added comment: PMID: 38129218: Thr144Met, listed as ACMG-P, hom in 1x pt with mito complex I deficiency and leukodystrophy, no functional studies, both parents are het. However, this variant has 2 homozygotes in gnomADv4, so unlikely pathogenic.; Changed publications: 22200994, 38129218
Intellectual disability syndromic and non-syndromic v0.5695 TAF1C Elena Savva Phenotypes for gene: TAF1C were changed from Global developmental delay; Intellectual disability; Spasticity; Strabismus; Seizures; Abnormality of nervous system morphology to Neurodevelopmental disorder (MONDO#0700092), TAF1C-related
Intellectual disability syndromic and non-syndromic v0.5694 CSTF2 Zornitza Stark Phenotypes for gene: CSTF2 were changed from Intellectual disability to Intellectual developmental disorder, X-linked 113, MIM# 301116
Intellectual disability syndromic and non-syndromic v0.5693 CSTF2 Zornitza Stark edited their review of gene: CSTF2: Changed phenotypes: Intellectual developmental disorder, X-linked 113, MIM# 301116
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Marked gene: ASCC3 as ready
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Gene: ascc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Classified gene: ASCC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5693 ASCC3 Zornitza Stark Gene: ascc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5692 ASCC3 Zornitza Stark gene: ASCC3 was added
gene: ASCC3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: ASCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC3 were set to 21937992; 35047834
Phenotypes for gene: ASCC3 were set to Intellectual developmental disorder, autosomal recessive 81, MIM# 620700
Review for gene: ASCC3 was set to GREEN
Added comment: Combined neuromuscular and neurobehavioral phenotype.

11 individuals from 7 unrelated families with homozygous (missense) or compound heterozygous variants (missense with a presumed LoF variant or 2 missense, no biallelic LoF) with a neurologic phenotype that ranges from severe developmental delay to muscle fatigue
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5691 GIGYF1 Zornitza Stark Phenotypes for gene: GIGYF1 were changed from Autism, Intellectual disability, GIGYF1-related (MONDO#0001071) to Autism spectrum disorder (MONDO:0005258), GIGYF1-related
Intellectual disability syndromic and non-syndromic v0.5690 SYN1 Zornitza Stark Mode of inheritance for gene: SYN1 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5689 HNRNPC Zornitza Stark Phenotypes for gene: HNRNPC were changed from Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related to intellectual developmental disorder-74, MIM#620688
Intellectual disability syndromic and non-syndromic v0.5688 HNRNPC Zornitza Stark edited their review of gene: HNRNPC: Changed phenotypes: intellectual developmental disorder-74, MIM#620688
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Marked gene: WDR44 as ready
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Gene: wdr44 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Classified gene: WDR44 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5688 WDR44 Zornitza Stark Gene: wdr44 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5687 WDR44 Zornitza Stark gene: WDR44 was added
gene: WDR44 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Review for gene: WDR44 was set to GREEN
Added comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.
WDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.
The studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Marked gene: ACACA as ready
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Classified gene: ACACA as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5686 ACACA Zornitza Stark Gene: acaca has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5685 ACACA Zornitza Stark gene: ACACA was added
gene: ACACA was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACACA were set to 34552920; 10677481; 16717184; 36709796
Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency, MIM# 613933
Review for gene: ACACA was set to AMBER
Added comment: Two families with molecular testing, missense variants, supportive functional data.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Marked gene: SP9 as ready
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Classified gene: SP9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5684 SP9 Zornitza Stark Gene: sp9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5683 SP9 Suliman Khan gene: SP9 was added
gene: SP9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SP9 were set to PMID: 38288683
Phenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: SP9 was set to GREEN
Added comment: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Marked gene: CAMK2D as ready
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Classified gene: CAMK2D as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5683 CAMK2D Elena Savva Gene: camk2d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5682 CAMK2D Elena Savva gene: CAMK2D was added
gene: CAMK2D was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CAMK2D were set to PMID: 38272033
Phenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related
Review for gene: CAMK2D was set to GREEN
Added comment: PMID: 38272033
- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old
- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological
- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5681 RBMX Zornitza Stark Phenotypes for gene: RBMX were changed from Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238 to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238; Gustavson syndrome, MIM# 309555
Intellectual disability syndromic and non-syndromic v0.5680 RBMX Zornitza Stark Publications for gene: RBMX were set to 25256757; 34260915
Intellectual disability syndromic and non-syndromic v0.5679 RBMX Zornitza Stark edited their review of gene: RBMX: Added comment: PMID 37277488: In-frame deletion reported in a large multiplex Swedish family; Changed publications: 25256757, 34260915, 37277488; Changed phenotypes: Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238, Gustavson syndrome, MIM# 309555
Intellectual disability syndromic and non-syndromic v0.5679 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573), PLA2G16-related to Lipodystrophy, familial partial, type 9, MIM# 620683
Intellectual disability syndromic and non-syndromic v0.5678 JMJD1C Elena Savva Phenotypes for gene: JMJD1C were changed from Intellectual disability to Intellectual disability (MONDO#0001071), JMJD1C-related
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Marked gene: CRELD1 as ready
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Classified gene: CRELD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5677 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5676 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type MIM#616462 to Acrofacial dysostosis, Cincinnati type MIM#616462; Leukodystrophy, hypomyelinating, 27, MIM# 620675
Intellectual disability syndromic and non-syndromic v0.5675 POLR1A Zornitza Stark Mode of inheritance for gene: POLR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5674 POLR1A Zornitza Stark reviewed gene: POLR1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 27, MIM# 620675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5674 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5673 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971 to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5673 ATP6V0A1 Elena Savva Phenotypes for gene: ATP6V0A1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-related to Developmental and epileptic encephalopathy 104 MIM#619970; Neurodevelopmental disorder with epilepsy and brain atrophy MIM#619971
Intellectual disability syndromic and non-syndromic v0.5672 KIF4A Elena Savva Phenotypes for gene: KIF4A were changed from Mental retardation, X-linked 100, MIM# 300923 to Intellectual developmental disorder, X-linked 100 MIM#300923
Intellectual disability syndromic and non-syndromic v0.5671 KCTD13 Elena Savva Mode of inheritance for gene: KCTD13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5670 KCTD13 Elena Savva Phenotypes for gene: KCTD13 were changed from Intellectual disability to Neurodevelopmental disorder (MONDO#0700092), KCTD13-related
Intellectual disability syndromic and non-syndromic v0.5669 KCNN3 Elena Savva Phenotypes for gene: KCNN3 were changed from Zimmermann-Laband syndrome 3; OMIM# 618658 to Zimmermann-Laband syndrome 3 MIM#618658
Intellectual disability syndromic and non-syndromic v0.5668 JAKMIP1 Elena Savva Phenotypes for gene: JAKMIP1 were changed from Intellectual disability; Seizures to Neurodevelopmental disorder (MONDO#0700092), JAKMIP1-related
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Marked gene: PPFIA3 as ready
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Classified gene: PPFIA3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5667 PPFIA3 Zornitza Stark Gene: ppfia3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5666 PPFIA3 Zornitza Stark gene: PPFIA3 was added
gene: PPFIA3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPFIA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPFIA3 were set to 37034625
Phenotypes for gene: PPFIA3 were set to Neurodevelopmental disorder, MONDO:0700092, PPFIA3-related
Review for gene: PPFIA3 was set to GREEN
Added comment: 19 individuals with mono-allelic variants presenting with features including developmental delay, intellectual disability, hypotonia, micro/macrocephaly, autism, and epilepsy.

One individual with compound het variants: insufficient evidence for bi-allelic variants causing disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Marked gene: MAX as ready
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Classified gene: MAX as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5665 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Marked gene: ZRSR2 as ready
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Classified gene: ZRSR2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5664 ZRSR2 Zornitza Stark Gene: zrsr2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Marked gene: BORCS8 as ready
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Classified gene: BORCS8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5663 BORCS8 Zornitza Stark Gene: borcs8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Marked gene: CACHD1 as ready
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Classified gene: CACHD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5662 CACHD1 Zornitza Stark Gene: cachd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5661 MAX Rylee Peters gene: MAX was added
gene: MAX was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Syndromic disease (MONDO:0002254), MAX-related
Review for gene: MAX was set to GREEN
Added comment: Three individuals who each share a recurrent de novo germline variant in the MAX gene, resulting in a p.Arg60Gln substitution in the loop of the b-HLH-LZ domain.

Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development. Other phenotypes reported include intellectual disability, perianal abscesses, pectus carinatum, hypospadias, renal agenesis, single umbilical artery, flattened thoracic vertebrae.

Functional analysis of the p.Arg60Gln variant shows a significant increase in CCND2 protein and a more efficient heterodimerization with c-Myc resulting in an increase in transcriptional activity of c-Myc.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Marked gene: SOX8 as ready
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Classified gene: SOX8 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5661 SOX8 Zornitza Stark Gene: sox8 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 ZRSR2 Chris Ciotta gene: ZRSR2 was added
gene: ZRSR2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to PMID: 38158857
Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related
Review for gene: ZRSR2 was set to GREEN
Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies.
Six unrelated families with two truncating variants and functional studies:
- p.(Gly404GlufsTer23): detected in one family with 2x affected males
- p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 BORCS8 Lauren Rogers changed review comment from: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature; to: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 SOX8 Paul De Fazio changed review comment from: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted).
Sources: Literature; to: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 CACHD1 Suliman Khan gene: CACHD1 was added
gene: CACHD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to PMID: 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder MONDO:0800439
Penetrance for gene: CACHD1 were set to unknown
Review for gene: CACHD1 was set to GREEN
Added comment: PMID: 38158856 - Six affected individuals from four unrelated families with homozygous CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant). Excluding the two fatal cases, all other were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Seizure was reported in one case. Whole exome sequencing identified bi-allelic loss of function variants in the CACHD1 gene. In vitro human neural models of CACHD1 depletion displayed dysregulated of Wnt signaling in the developing brain.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 SOX8 Paul De Fazio gene: SOX8 was added
gene: SOX8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088
Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Review for gene: SOX8 was set to RED
gene: SOX8 was marked as current diagnostic
Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.

Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 BORCS8 Lauren Rogers gene: BORCS8 was added
gene: BORCS8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS8 were set to 38128568
Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Review for gene: BORCS8 was set to GREEN
Added comment: 3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants.

HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Marked gene: GTPBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Classified gene: GTPBP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5660 GTPBP1 Zornitza Stark Gene: gtpbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5659 GTPBP1 Lucy Spencer gene: GTPBP1 was added
gene: GTPBP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder (MONDO#0700092), GTPBP1-related
Review for gene: GTPBP1 was set to GREEN
Added comment: PMID: 38118446- Cohort of individuals with variants in GTPBP2 (which has been previously described) and GTPBP1 (new) who have an identical neurodevelopmental syndrome. 4 homozygous individuals from 3 consanguineous families. 2 families have different NMD-predicted nonsense variants and the third has a missense, all are absent from gnomad v4.

The shared cardinal features of GTPBP1 and 2 related disease are microcephaly, profound neurodevelopmental impairment, and distinctive craniofacial features. Epilepsy was present in 10 of 20 individuals but its not clear if those individuals had GTPBP1 or 2 variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5659 PUS3 Zornitza Stark Phenotypes for gene: PUS3 were changed from Mental retardation, autosomal recessive 55, MIM# 617051 to Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Intellectual disability syndromic and non-syndromic v0.5658 PUS3 Zornitza Stark edited their review of gene: PUS3: Changed phenotypes: Neurodevelopmental disorder with microcephaly and gray sclerae, MIM# 617051
Intellectual disability syndromic and non-syndromic v0.5658 ALG8 Zornitza Stark Publications for gene: ALG8 were set to 26066342
Intellectual disability syndromic and non-syndromic v0.5657 PRICKLE2 Zornitza Stark changed review comment from: LIMITED by ClinGen.; to: LIMITED by ClinGen; however, experimental evidence appears not to have been considered.
Intellectual disability syndromic and non-syndromic v0.5657 PRICKLE2 Zornitza Stark Phenotypes for gene: PRICKLE2 were changed from Neurodevelopmental disorder; global developmental delay; behavioural difficulties ± epilepsy; autistic features; attention deficit hyperactive disorder; psychiatric symptoms to Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related
Intellectual disability syndromic and non-syndromic v0.5656 PRICKLE2 Zornitza Stark Publications for gene: PRICKLE2 were set to PMID: 34092786
Intellectual disability syndromic and non-syndromic v0.5655 PRICKLE2 Zornitza Stark Classified gene: PRICKLE2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5655 PRICKLE2 Zornitza Stark Gene: prickle2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5654 PRICKLE2 Zornitza Stark reviewed gene: PRICKLE2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34092786, 21276947, 26942291, 26942292; Phenotypes: Neurodevelopmental disorder MONDO:0700092, PRICKLE2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5654 ERI1 Zornitza Stark Phenotypes for gene: ERI1 were changed from Intellectual disability (MONDO#0001071), ERI1-related to Hoxha-Aliu syndrome, MIM# 620662
Intellectual disability syndromic and non-syndromic v0.5653 ERI1 Zornitza Stark reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hoxha-Aliu syndrome, MIM# 620662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5653 ALG8 Rylee Peters reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35716054; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM# 608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5653 PDE2A Lauren Rogers reviewed gene: PDE2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32467598, 29392776, 37317634; Phenotypes: Intellectual developmental disorder with paroxysmal dyskinesia or seizures MIM#619150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5653 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from Syndromic disease, MONDO:0002254, RAP1B-related to Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Intellectual disability syndromic and non-syndromic v0.5652 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Thrombocytopenia 1 with multiple congenital anomalies and dysmorphic facies, MIM# 620654
Intellectual disability syndromic and non-syndromic v0.5652 GPT2 Zornitza Stark Phenotypes for gene: GPT2 were changed from Mental retardation, autosomal recessive 49, MIM#616281 to Neurodevelopmental disorder with microcephaly and spastic paraplegia, MIM# 616281
Intellectual disability syndromic and non-syndromic v0.5651 RAP1GDS1 Zornitza Stark Phenotypes for gene: RAP1GDS1 were changed from Intellectual disability; dysmorphic features to Alfadhel syndrome, MIM# 620655
Intellectual disability syndromic and non-syndromic v0.5650 RAP1GDS1 Zornitza Stark edited their review of gene: RAP1GDS1: Changed phenotypes: Alfadhel syndrome, MIM# 620655
Intellectual disability syndromic and non-syndromic v0.5650 CASP2 Zornitza Stark Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653
Intellectual disability syndromic and non-syndromic v0.5649 CASP2 Zornitza Stark reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM# 620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5649 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Intellectual disability syndromic and non-syndromic v0.5648 CAPRIN1 Zornitza Stark Phenotypes for gene: CAPRIN1 were changed from Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092 to Neurodevelopmental disorder, CAPRIN1-related MONDO:0700092; Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636
Intellectual disability syndromic and non-syndromic v0.5648 CAPRIN1 Zornitza Stark Publications for gene: CAPRIN1 were set to 35979925; 35977029; 28135719; 31398340
Intellectual disability syndromic and non-syndromic v0.5647 CAPRIN1 Zornitza Stark reviewed gene: CAPRIN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36136249; Phenotypes: Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, MIM# 620636; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Marked gene: MANF as ready
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Classified gene: MANF as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5647 MANF Zornitza Stark Gene: manf has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5646 MANF Zornitza Stark gene: MANF was added
gene: MANF was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: MANF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANF were set to 26077850; 33500254; 34815294
Phenotypes for gene: MANF were set to Diabetes, deafness, developmental delay, and short stature syndrome, MIM# 620651
Review for gene: MANF was set to AMBER
Added comment: Two individuals reported with homozygous variants. Mouse model recapitulates deafness phenotype.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5645 DRG1 Zornitza Stark Phenotypes for gene: DRG1 were changed from Neurodevelopmental disorder (MONDO:0700092), DRG1-related to Tan-Almurshedi syndrome, MIM# 620641
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Marked gene: GCDH as ready
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Gene: gcdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5644 GCDH Zornitza Stark Phenotypes for gene: GCDH were changed from to Glutaric aciduria, type I MIM#231670
Intellectual disability syndromic and non-syndromic v0.5643 GCDH Zornitza Stark Mode of inheritance for gene: GCDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5642 GCDH Zornitza Stark reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutaric aciduria, type I MIM#231670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Added comment: Comment when marking as ready: HGNC name is PLAAT3
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5642 PLA2G16 Zornitza Stark Tag new gene name tag was added to gene: PLA2G16.
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Marked gene: PRPF19 as ready
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Classified gene: PRPF19 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5642 PRPF19 Zornitza Stark Gene: prpf19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5641 PRPF19 Zornitza Stark gene: PRPF19 was added
gene: PRPF19 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRPF19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF19 were set to 37962958
Phenotypes for gene: PRPF19 were set to Neurodevelopmental disorder (MONDO:0700092), PRPF19-related
Review for gene: PRPF19 was set to GREEN
Added comment: PMID: 37962958 Six unrelated individuals with de novo variants. Five had speech language motor delay, four had formal diagnosis of autism, three hypotonia and one fetus with multiple congenital abnormalities.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5641 PRPF19 Zornitza Stark gene: PRPF19 was added
gene: PRPF19 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRPF19 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF19 were set to 37962958
Phenotypes for gene: PRPF19 were set to Neurodevelopmental disorder (MONDO:0700092), PRPF19-related
Review for gene: PRPF19 was set to GREEN
Added comment: PMID: 37962958 Six unrelated individuals with de novo variants. Five had speech language motor delay, four had formal diagnosis of autism, three hypotonia and one fetus with multiple congenital abnormalities.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Marked gene: PLA2G16 as ready
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5640 PLA2G16 Zornitza Stark Phenotypes for gene: PLA2G16 were changed from Lipodystrophy (MONDO:0006573) to Lipodystrophy (MONDO:0006573), PLA2G16-related
Intellectual disability syndromic and non-syndromic v0.5639 PLA2G16 Zornitza Stark Mode of inheritance for gene: PLA2G16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5638 PLA2G16 Zornitza Stark Classified gene: PLA2G16 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5638 PLA2G16 Zornitza Stark Gene: pla2g16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5637 RAB1A Zornitza Stark Phenotypes for gene: RAB1A were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to neurodevelopmental disorder MONDO:0700092, RAB1A-related
Intellectual disability syndromic and non-syndromic v0.5636 RAB1A Zornitza Stark Classified gene: RAB1A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5636 RAB1A Zornitza Stark Gene: rab1a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5635 FUK Zornitza Stark Marked gene: FUK as ready
Intellectual disability syndromic and non-syndromic v0.5635 FUK Zornitza Stark Added comment: Comment when marking as ready: Promoted to Green with the additional cases.
Intellectual disability syndromic and non-syndromic v0.5635 FUK Zornitza Stark Gene: fuk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5635 FUK Zornitza Stark Publications for gene: FUK were set to 30503518
Intellectual disability syndromic and non-syndromic v0.5634 FUK Zornitza Stark Classified gene: FUK as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5634 FUK Zornitza Stark Gene: fuk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5633 SV2A Zornitza Stark Marked gene: SV2A as ready
Intellectual disability syndromic and non-syndromic v0.5633 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5633 SV2A Zornitza Stark Phenotypes for gene: SV2A were changed from Epilepsy, MONDO:0005027; microcephaly MONDO:0001149; intellectual disability MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092, SV2A-related
Intellectual disability syndromic and non-syndromic v0.5632 SV2A Zornitza Stark Classified gene: SV2A as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5632 SV2A Zornitza Stark Gene: sv2a has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5631 SV2A Karina Sandoval gene: SV2A was added
gene: SV2A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SV2A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SV2A were set to PMID: 37985816
Phenotypes for gene: SV2A were set to Epilepsy, MONDO:0005027; microcephaly MONDO:0001149; intellectual disability MONDO:0001071
Review for gene: SV2A was set to AMBER
Added comment: Monoallelic variants cause epilepsy. Biallelic variant in this 5yo with p.Arg289Ter and another 5yo from another paper with homozygous p.Arg383Gln, reported to cause severe phenotype of drug-resistant epileptic encephalopathy with microcephaly, DD, movement disorder and growth retardation.
This paper references 5 other families with both AR & AD
Family #1 – p.Arg383Gln, AR, 2 affected in family, parents healthy carriers
Family #2 – p.Arg570Cys, AD, 2 affected, inherited from affected mother (in gnomAD v2 1 het, absent from gnomAD v3)
Family #3 – p.Gly660Arg, AD, de novo
Family #4 – p.Gly660Arg, AD, segregated in 11 family members
Family #5 (this study) – p.Arg289Ter, AR, parents and 2 sibs asymptomatic carriers
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5631 FUK Lisa Norbart reviewed gene: FUK: Rating: AMBER; Mode of pathogenicity: None; Publications: (PMID: 35718084, 36426412); Phenotypes: Congenital disorder of glycosylation with defective fucosylation 2 (MIM#618324); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5631 CRELD1 Naomi Baker gene: CRELD1 was added
gene: CRELD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CRELD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRELD1 were set to PMID: 37947183
Phenotypes for gene: CRELD1 were set to Neurodevelopmental disorder (MONDO:0700092), CRELD1-related
Review for gene: CRELD1 was set to GREEN
Added comment: Publication reports 18 individuals from 14 unrelated families affected by biallelic recessive variants in CRELD1, presenting with early-onset neurodevelopmental features, most notably hypotonia and epilepsy, with developmental plateauing and slowly progressive nonneurologic medical complexities in survivors, including cardiac rhythm disturbances and frequent infections. Most individuals have a missense variant in trans with a putative null allele. Four variants were re-current: p.(Cys192Tyr) in 10 families, p.(Gln320Argfs) in 5 families, p.(Ala377Thrfs) in 2 families, and p.(Met369Val) also in 2 families. Some functional studies also reported (Xenopus tropicalis).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5631 RAB1A Chris Ciotta gene: RAB1A was added
gene: RAB1A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAB1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB1A were set to PMID: 37924809
Phenotypes for gene: RAB1A were set to neurodevelopmental disorder MONDO:0700092, CASP2-related
Review for gene: RAB1A was set to AMBER
Added comment: 4 families and 5 individuals, 2/5 have speech delay and 4/5 have motor delay.
Anxiety in 3/5 and autism in 2/5. Microcephaly in only one individual, spastic paraplegia observed in 2 individuals from one family.
In 2 families variants were inherited from an affected parent.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5631 DDX17 Elena Savva Classified gene: DDX17 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5631 DDX17 Elena Savva Gene: ddx17 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5630 DDX17 Elena Savva Classified gene: DDX17 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5630 DDX17 Elena Savva Gene: ddx17 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5629 DDX17 Elena Savva Marked gene: DDX17 as ready
Intellectual disability syndromic and non-syndromic v0.5629 DDX17 Elena Savva Gene: ddx17 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Marked gene: MARK4 as ready
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Gene: mark4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Phenotypes for gene: MARK4 were changed from neurodevelopmental disorder (MONDO:0700092), MARK4-related to Neurodevelopmental disorder (MONDO:0700092), MARK4-related
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Classified gene: MARK4 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5629 MARK4 Elena Savva Gene: mark4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers reviewed gene: PLA2G16: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37919452; Phenotypes: Lipodystrophy (MONDO:0006573); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers Deleted their review
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers reviewed gene: PLA2G16: Rating: ; Mode of pathogenicity: None; Publications: PMID: 37919452; Phenotypes: Lipodystrophy (MONDO:0006573); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers Deleted their review
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers reviewed gene: PLA2G16: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37919452; Phenotypes: Lipodystrophy (MONDO:0006573); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers Deleted their review
Intellectual disability syndromic and non-syndromic v0.5628 PLA2G16 Lauren Rogers gene: PLA2G16 was added
gene: PLA2G16 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PLA2G16 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PLA2G16 were set to PMID: 37919452
Phenotypes for gene: PLA2G16 were set to Lipodystrophy (MONDO:0006573)
Added comment: 7 patients from 4 unrelated consanguineous families with homozygous loss of function PTC variants. Features: 4/7 metabolic features, 6/7 neurological/skeletal features, 3/7 Psychomotor retardation/intellectual disability, 5/7 demyelinating peripheral neuropathy.

Null mouse and patient derived white adipose tissue showed enrichment of arachidonic acid-containing membrane phospholipids and a strong decrease in PPARγ. CRISPR–Cas9-mediated PLAAT3 inactivation in human adipose stem cells induced insulin resistance, altered adipocyte differentiation with decreased lipid droplet formation and reduced the expression of adipogenic and mature adipocyte markers, including PPARγ.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5628 PPID Elena Savva Marked gene: PPID as ready
Intellectual disability syndromic and non-syndromic v0.5628 PPID Elena Savva Gene: ppid has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5628 MARK4 Rylee Peters changed review comment from: Missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature; to: Heterozygous missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5628 SEL1L Zornitza Stark Marked gene: SEL1L as ready
Intellectual disability syndromic and non-syndromic v0.5628 SEL1L Zornitza Stark Gene: sel1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5628 SEL1L Zornitza Stark Classified gene: SEL1L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5628 SEL1L Zornitza Stark Gene: sel1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5627 DDX17 Melanie Marty gene: DDX17 was added
gene: DDX17 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DDX17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX17 were set to https://www.medrxiv.org/search/DDX17
Phenotypes for gene: DDX17 were set to Neurodevelopmental disorder (MONDO#0700092), DDX17-related
Review for gene: DDX17 was set to GREEN
Added comment: https://www.medrxiv.org/search/DDX17 (pre-print)
11 patients with het de novo variants in DDX17 (5 NMD, 6 missense). Patient's phenotype included mild-moderate intellectual disability, delayed speech and language development and global developmental delay. 64% had dysmorphic facial features. Some patients also have gross and fine motor delay, generalized hypotonia, stereotypy, and evidence of autism spectrum disorder.

Knockdown of Ddx17 in newborn mice showed impaired axon outgrowth and reduced axon outgrowth and branching was observed in primary cortical neurons in vitro. This result was replicated in Crispant Xenopus tadpoles, which had clear functional neural defects and showed an impaired neurobehavioral phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5627 MARK4 Rylee Peters gene: MARK4 was added
gene: MARK4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MARK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK4 were set to PMID: 38041405
Phenotypes for gene: MARK4 were set to neurodevelopmental disorder (MONDO:0700092), MARK4-related
Mode of pathogenicity for gene: MARK4 was set to Other
Review for gene: MARK4 was set to AMBER
gene: MARK4 was marked as current diagnostic
Added comment: Missense variant, c.604T>C; p.Phe202Leu, identified in two siblings with childhood-onset neurodevelopmental disorder characterised by global developmental delay, intellectual disability, behavioural abnormalities, and dysmorphic features. The variant is located in the catalytic domain of the kinase, and is inherited from unaffected mosaic mother.

Functional investigation revealed that the variant results in a gain-of-function in the ability of MARK4 to phosphorylate tau and leads to up-regulation of the mTORC1 pathway.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5627 SEL1L Sarah Pantaleo gene: SEL1L was added
gene: SEL1L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SEL1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEL1L were set to PMID: 37943610; PMID: 37943617
Phenotypes for gene: SEL1L were set to Neurodevelopmental disorder, MONDO:0700092, SEL1L-related
Penetrance for gene: SEL1L were set to Complete
Review for gene: SEL1L was set to GREEN
Added comment: Wang paper PMID: 37943610

SEL1L protein is involved in the SEL1L-HRD1 endoplasmic reticulum (ER)-associated degradation.

Report two biallelic missense variants in SEL1L in six children from three independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia and/or ataxia (termed ERAD-associated neurodevelopment disorder with onset in infancy (ENDI). The variants were hypomorphic and impaired ERAD function.

Identified by WES. Parents heterozygous and asymptomatic. P.(Gly585Asp) in Patient 1, p.(Met528Arg) in Patients 2 and 3 (siblings).

All variants cause substrate accumulation. The extent of substrate accumulation in knockin cells was modest compared to those in knockout cells, pointing to a hypomorphic nature.

They also had a variant in HRD1.



Weis paper PMID: 37943617

Third variant p.(Cys141Tyr), biallelic, causing premature death in five patients from a consanguineous family with early-onset neurodevelopmental disorders and agammaglobulinaemia due to severe SEL1L-HRD1 ERAD dysfunction.

This variant appears to have a more severe outcome, exhibiting B cell depletion and agammaglobulinaemia, causing the most severe dysfunction among all of the variants described by this group so far. They postulate that functionality of SEL1L-HRD1 ERAD is inversely correlated with disease severity in humans.

Their symptoms were dev delay, neurological disorder and agammaglobulinaemia in childhood. Along with severe axial hypotonia, short stature and microcephaly.

“Not a complete loss-of-function variant”.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5627 RBFOX1 Zornitza Stark Phenotypes for gene: RBFOX1 were changed from Intellectual disability; autism to Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related
Intellectual disability syndromic and non-syndromic v0.5626 RBFOX1 Zornitza Stark Publications for gene: RBFOX1 were set to 24664471
Intellectual disability syndromic and non-syndromic v0.5625 RBFOX1 Zornitza Stark Classified gene: RBFOX1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5625 RBFOX1 Zornitza Stark Gene: rbfox1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5624 RBFOX1 Dean Phelan reviewed gene: RBFOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37962958; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), RBFOX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5624 PPID Elena Savva gene: PPID was added
gene: PPID was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PPID was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPID were set to 37977818
Phenotypes for gene: PPID were set to Stutter disorder, (MONDO:0000723), PPID-related
Review for gene: PPID was set to RED
Added comment: PMID: 37977818 - a large family (10 affected confirmed to have the variant) with stuttering/language disorder and a het missense (p.(Pro270Ser)). Mouse K/I model showed microstructural changes in the corticospinal tract
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5623 GRIA3 Zornitza Stark Publications for gene: GRIA3 were set to 32977175; 17989220
Intellectual disability syndromic and non-syndromic v0.5622 GRIA3 Zornitza Stark Mode of inheritance for gene: GRIA3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5621 GRIA3 Zornitza Stark reviewed gene: GRIA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 38038360; Phenotypes: Intellectual developmental disorder, X-linked, syndromic, Wu type (MIM#300699); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5621 TRAPPC4 Zornitza Stark Phenotypes for gene: TRAPPC4 were changed from intellectual disability; epilepsy; spasticity; microcephaly to Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, MIM# 618741
Intellectual disability syndromic and non-syndromic v0.5620 TRAPPC4 Zornitza Stark edited their review of gene: TRAPPC4: Changed phenotypes: Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, MIM# 618741
Intellectual disability syndromic and non-syndromic v0.5620 WBP4 Zornitza Stark Publications for gene: WBP4 were set to
Intellectual disability syndromic and non-syndromic v0.5619 WBP4 Zornitza Stark reviewed gene: WBP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 37963460; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, WBP4-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5619 WNK3 Zornitza Stark Phenotypes for gene: WNK3 were changed from Neurodevelopmental disorder, WNK3-related (MONDO#0700092) to Prieto syndrome, MIM# 309610
Intellectual disability syndromic and non-syndromic v0.5618 WNK3 Zornitza Stark reviewed gene: WNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Prieto syndrome, MIM# 309610; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5618 WDR11 Elena Savva Mode of inheritance for gene: WDR11 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5617 DOT1L Zornitza Stark Marked gene: DOT1L as ready
Intellectual disability syndromic and non-syndromic v0.5617 DOT1L Zornitza Stark Gene: dot1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5617 DOT1L Zornitza Stark Classified gene: DOT1L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5617 DOT1L Zornitza Stark Gene: dot1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5616 DOT1L Zornitza Stark gene: DOT1L was added
gene: DOT1L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DOT1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOT1L were set to 37827158
Phenotypes for gene: DOT1L were set to Neurodevelopmental disorder, MONDO:0700092, DOT1L-related
Mode of pathogenicity for gene: DOT1L 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: DOT1L was set to GREEN
Added comment: Nine individuals reported with seven de novo missense variants.

All had DD/ID and variable patterns of associated congenital anomalies.

Variants demonstrated to be GoF and lead to increased H3K79 methylation levels in flies and human cells.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5615 PBX1 Zornitza Stark Marked gene: PBX1 as ready
Intellectual disability syndromic and non-syndromic v0.5615 PBX1 Zornitza Stark Gene: pbx1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5615 PBX1 Zornitza Stark Phenotypes for gene: PBX1 were changed from to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641
Intellectual disability syndromic and non-syndromic v0.5614 PBX1 Zornitza Stark Mode of inheritance for gene: PBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5613 PBX1 Chirag Patel reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5613 KCNJ11 Chirag Patel Classified gene: KCNJ11 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5613 KCNJ11 Chirag Patel Gene: kcnj11 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5612 KCNJ11 Chirag Patel reviewed gene: KCNJ11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5612 KCNA3 Zornitza Stark Publications for gene: KCNA3 were set to
Intellectual disability syndromic and non-syndromic v0.5611 KCNA3 Zornitza Stark reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37964487; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KCNA3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5611 FOXP4 Elena Savva Phenotypes for gene: FOXP4 were changed from Neurodevelopmental disorder (MONDO#0700092), FOXP4-related to Neurodevelopmental disorder (MONDO#0700092), FOXP4-related
Intellectual disability syndromic and non-syndromic v0.5611 FOXP4 Elena Savva Phenotypes for gene: FOXP4 were changed from Neurodevelopmental disorder (MONDO#0700092), FOXP4-related to Neurodevelopmental disorder (MONDO#0700092), FOXP4-related
Intellectual disability syndromic and non-syndromic v0.5610 FOXP4 Elena Savva Phenotypes for gene: FOXP4 were changed from Neurodevelopmental disorder; multiple congenital abnormalities to Neurodevelopmental disorder (MONDO#0700092), FOXP4-related
Intellectual disability syndromic and non-syndromic v0.5609 FOXP4 Elena Savva Publications for gene: FOXP4 were set to 33110267
Intellectual disability syndromic and non-syndromic v0.5609 FOXP4 Elena Savva Classified gene: FOXP4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5609 FOXP4 Elena Savva Gene: foxp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5608 DLG2 Zornitza Stark Tag SV/CNV tag was added to gene: DLG2.
Intellectual disability syndromic and non-syndromic v0.5608 VCP Zornitza Stark Marked gene: VCP as ready
Intellectual disability syndromic and non-syndromic v0.5608 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5608 VCP Zornitza Stark Classified gene: VCP as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5608 VCP Zornitza Stark Gene: vcp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5607 HIST1H4J Zornitza Stark Publications for gene: HIST1H4J were set to 31804630
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4J Zornitza Stark Marked gene: HIST1H4J as ready
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4J Zornitza Stark Added comment: Comment when marking as ready: New gene name: H4C11
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4J Zornitza Stark Gene: hist1h4j has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4J Zornitza Stark Tag new gene name tag was added to gene: HIST1H4J.
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4I Zornitza Stark Marked gene: HIST1H4I as ready
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4I Zornitza Stark Added comment: Comment when marking as ready: New gene name: H4C9
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4I Zornitza Stark Gene: hist1h4i has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4I Zornitza Stark Tag new gene name tag was added to gene: HIST1H4I.
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4F Zornitza Stark Marked gene: HIST1H4F as ready
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4F Zornitza Stark Added comment: Comment when marking as ready: New gene name H4C6
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4F Zornitza Stark Gene: hist1h4f has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4F Zornitza Stark Tag new gene name tag was added to gene: HIST1H4F.
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4E Zornitza Stark Tag new gene name tag was added to gene: HIST1H4E.
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4D Zornitza Stark Tag new gene name tag was added to gene: HIST1H4D.
Intellectual disability syndromic and non-syndromic v0.5606 HIST1H4C Zornitza Stark Tag new gene name tag was added to gene: HIST1H4C.
Intellectual disability syndromic and non-syndromic v0.5606 VCP Manny Jacobs gene: VCP was added
gene: VCP was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to PMID: 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 syndromic and non-syndromic v0.5606 AGPAT3 Elena Savva Classified gene: AGPAT3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5606 AGPAT3 Elena Savva Gene: agpat3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5605 AGPAT3 Elena Savva Classified gene: AGPAT3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5605 AGPAT3 Elena Savva Gene: agpat3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5605 AGPAT3 Elena Savva Marked gene: AGPAT3 as ready
Intellectual disability syndromic and non-syndromic v0.5605 AGPAT3 Elena Savva Gene: agpat3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5605 AGPAT3 Elena Savva Classified gene: AGPAT3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5605 AGPAT3 Elena Savva Gene: agpat3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5604 ELP1 Ain Roesley Marked gene: ELP1 as ready
Intellectual disability syndromic and non-syndromic v0.5604 ELP1 Ain Roesley Gene: elp1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5604 ELP1 Ain Roesley Classified gene: ELP1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5604 ELP1 Ain Roesley Gene: elp1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5603 AGPAT3 Ee Ming Wong changed review comment from: - 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; to: - 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 syndromic and non-syndromic v0.5603 SGSM3 Ain Roesley Marked gene: SGSM3 as ready
Intellectual disability syndromic and non-syndromic v0.5603 SGSM3 Ain Roesley Gene: sgsm3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5603 SGSM3 Ain Roesley Classified gene: SGSM3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5603 SGSM3 Ain Roesley Gene: sgsm3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5602 SGSM3 Ain Roesley Tag founder tag was added to gene: SGSM3.
Intellectual disability syndromic and non-syndromic v0.5602 SGSM3 Dean Phelan gene: SGSM3 was added
gene: SGSM3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SGSM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGSM3 were set to PMID: 37833060
Phenotypes for gene: SGSM3 were set to Neurodevelopmental disorder (MONDO:0700092), SGSM3-related
Review for gene: SGSM3 was set to GREEN
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 prevalent phenotypes 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 syndromic and non-syndromic v0.5602 AGPAT3 Ee Ming Wong gene: AGPAT3 was added
gene: AGPAT3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AGPAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGPAT3 were set to PMID: 37821758
Phenotypes for gene: AGPAT3 were set to Neurodevelopmental disorder (MONDO#0700092), AGPAT3-related
Review for gene: AGPAT3 was set to GREEN
gene: AGPAT3 was marked as current diagnostic
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 syndromic and non-syndromic v0.5602 DLG2 Elena Savva Classified gene: DLG2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5602 DLG2 Elena Savva Gene: dlg2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5601 DLG2 Elena Savva Marked gene: DLG2 as ready
Intellectual disability syndromic and non-syndromic v0.5601 DLG2 Elena Savva Gene: dlg2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5601 DLG2 Elena Savva gene: DLG2 was added
gene: DLG2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLG2 were set to PMID: 37860969
Phenotypes for gene: DLG2 were set to Intellectual disability (MONDO#0001071), DLG2-related
Review for gene: DLG2 was set to AMBER
Added comment: PMID: 37860969 - 13 patients from 10 families with neurodevelopmental disorders, dysmorphic features and intragenic deletions including both exonic (minimal affect all transcripts) and UTR regions.
Majority of variants were inherited, some de novo. But many NMD PTCs in gnomAD (some looking messy, in noncanonical transcript etc.)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5600 CASP2 Ain Roesley Marked gene: CASP2 as ready
Intellectual disability syndromic and non-syndromic v0.5600 CASP2 Ain Roesley Gene: casp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5600 CASP2 Ain Roesley Classified gene: CASP2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5600 CASP2 Ain Roesley Gene: casp2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5599 CASP2 Ain Roesley gene: CASP2 was added
gene: CASP2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CASP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP2 were set to 37880421
Phenotypes for gene: CASP2 were set to neurodevelopmental disorder MONDO:0700092, CASP2-related
Penetrance for gene: CASP2 were set to Complete
Review for gene: CASP2 was set to GREEN
gene: CASP2 was marked as current diagnostic
Added comment: 7 patients from 5 families
4 families hom for PTCs, 1 family Chet for splice+PTC
RNA studies done for the splice to indicate usage of 2 cryptic splice donor sites

5/5 have ID/dev delay
1/5 has seizures
2/5 hypotonia
3/5 lissencephaly (pachygyria and cortical thickening)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5598 ELP1 Sarah Pantaleo gene: ELP1 was added
gene: ELP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ELP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ELP1 were set to PMID: 36864284
Phenotypes for gene: ELP1 were set to Neurodevelopmental disorder, MONDO:0700092, ELP1-related
Review for gene: ELP1 was set to RED
Added comment: “A novel ELP1 mutation impairs the function of the Elongator complex and causes a severe neurodevelopment disorder”.

The Elongator complex is suggested to play a role in NDDs, given that patient-derived mutations in its ELP2, ELP3, ELP4 and ELP6 subunits have been associated with these disorders.

Pathogenic variants in ELP1 have been previously found in familial dysautonomia and medulloblastoma, with no link to NDDs affecting primarily the central nervous system.

Clinical investigation included patient history and physical, neurological and MRI. A novel homozygous likely pathogenic ELP1 variant was identified by WGS (absent from gnomAD). Functional studies included in silico analysis of the mutated ELP1 in the context of the holo-complex, production and purification of the ELP1 harbouring the identified mutation and in vitro analyses.

Report a novel missense mutation in the ELP1 identified in two siblings with ID and GDD (both less than 10 years old). The mutation is shown to perturb the ability of ELP123 to bind tRNAs and compromises the function of the Elongator in vitro and in human cells.

Both sibling are non-verbal and had severe ID/GDD. MRI revealed white matter lesions with enlarged perivascular spaces, suggestive of an inflammatory reaction associate with demyelination. WGS identified c.2444A>C; p.(Lys815Thr), homozygous in both siblings. Consanguineous family. Parents heterozygous and asymptomatic. Carry out significant functional studies.

Conclude that screening for ELP1 mutations “may be beneficial”.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5598 AXIN1 Zornitza Stark Phenotypes for gene: AXIN1 were changed from Syndromic disease, (MONDO:0002254), AXIN1-related to Craniometadiaphyseal osteosclerosis with hip dysplasia, MIM# 620558
Intellectual disability syndromic and non-syndromic v0.5597 AXIN1 Zornitza Stark changed review comment from: Intellectual disability is a feature.; to: Developmental delay is a feature.
Intellectual disability syndromic and non-syndromic v0.5597 AXIN1 Zornitza Stark reviewed gene: AXIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniometadiaphyseal osteosclerosis with hip dysplasia, MIM# 620558; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5597 KDM5B Zornitza Stark Phenotypes for gene: KDM5B were changed from Mental retardation, autosomal recessive 65 MIM#618109; Intellectual disability and/or autism, autosomal dominant to Mental retardation, autosomal recessive 65 MIM#618109; Neurodevelopmental disorder (MONDO#0700092), KDM5B-related, autosomal dominant
Intellectual disability syndromic and non-syndromic v0.5596 KDM5B Lauren Rogers reviewed gene: KDM5B: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), KDM5B-related, Intellectual developmental disorder, autosomal recessive 65 (MIM#618109); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5596 PTPN4 Bryony Thompson Publications for gene: PTPN4 were set to 17953619; 25424712; 30238967; DOI: https://doi.org/10.1016/j.xhgg.2021.100033
Intellectual disability syndromic and non-syndromic v0.5595 PTPN4 Bryony Thompson changed review comment from: >3 unrelated probands and supporting mouse model
PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity
PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder
PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines
DOI: https://doi.org/10.1016/j.xhgg.2021.100033 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo.
Sources: Literature; to: >3 unrelated probands and supporting mouse model
PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity
PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder
PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines
PMID: 34527963 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5595 PTPN4 Bryony Thompson edited their review of gene: PTPN4: Changed publications: 17953619, 25424712, 30238967, 34527963
Intellectual disability syndromic and non-syndromic v0.5595 ZFHX3 Zornitza Stark Phenotypes for gene: ZFHX3 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, ZFHX3-related
Intellectual disability syndromic and non-syndromic v0.5594 ZFHX3 Zornitza Stark Publications for gene: ZFHX3 were set to
Intellectual disability syndromic and non-syndromic v0.5593 COG3 Zornitza Stark Phenotypes for gene: COG3 were changed from Neurodevelopmental disorder (MONDO#0700092), COG3-related to Congenital disorder of glycosylation, type IIbb, MIM# 620546
Intellectual disability syndromic and non-syndromic v0.5592 COG3 Zornitza Stark reviewed gene: COG3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIbb, MIM# 620546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5592 ZFHX3 Chirag Patel Classified gene: ZFHX3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5592 ZFHX3 Chirag Patel Gene: zfhx3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5591 ZFHX3 Chirag Patel edited their review of gene: ZFHX3: Added comment: 41 patients with protein truncating variants (PTVs) or (partial) deletions of ZFHX3. Presentations included (mild) ID and/or behavioural problems, postnatal growth retardation, feeding difficulties, dysmorphism (rarely cleft palate). Nuclear abundance of ZFHX3 increases during human brain development and neuronal differentiation in neural stem cells and SH-SY5Y cells, ZFHX3 interacts with the chromatin remodelling BRG1/Brm-associated factor complex and the cleavage and polyadenylation complex. ZFHX3 haploinsufficiency associates with a specific DNA methylation profile in leukocyte-derived DNA, and participates in chromatin remodelling and mRNA processing.; Changed rating: GREEN; Changed publications: PMID: 37292950; Changed phenotypes: Neurodevelopmental disorder; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Set current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5591 KDM2B Ain Roesley edited their review of gene: KDM2B: Changed phenotypes: neurodevelopmental disorder MONDO#0700092, KDM2B-related
Intellectual disability syndromic and non-syndromic v0.5591 KDM2B Ain Roesley Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder MONDO#070009, KDM2B-related to neurodevelopmental disorder MONDO#0700092, KDM2B-related
Intellectual disability syndromic and non-syndromic v0.5590 ZNF148 Zornitza Stark Marked gene: ZNF148 as ready
Intellectual disability syndromic and non-syndromic v0.5590 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5590 B4GALNT1 Zornitza Stark Marked gene: B4GALNT1 as ready
Intellectual disability syndromic and non-syndromic v0.5590 B4GALNT1 Zornitza Stark Gene: b4galnt1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5590 B4GALNT1 Zornitza Stark Phenotypes for gene: B4GALNT1 were changed from to Spastic paraplegia 26, autosomal recessive (MIM #609195)
Intellectual disability syndromic and non-syndromic v0.5589 B4GALNT1 Zornitza Stark Mode of inheritance for gene: B4GALNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5588 B4GALNT1 Zornitza Stark reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 26, autosomal recessive (MIM #609195); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5588 AUH Zornitza Stark Marked gene: AUH as ready
Intellectual disability syndromic and non-syndromic v0.5588 AUH Zornitza Stark Gene: auh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5588 AUH Zornitza Stark Phenotypes for gene: AUH were changed from to 3-methylglutaconic aciduria, type I, MIM# 250950
Intellectual disability syndromic and non-syndromic v0.5587 AUH Zornitza Stark Mode of inheritance for gene: AUH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5586 AUH Zornitza Stark reviewed gene: AUH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria, type I, MIM# 250950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5586 ATP6V0A2 Zornitza Stark Marked gene: ATP6V0A2 as ready
Intellectual disability syndromic and non-syndromic v0.5586 ATP6V0A2 Zornitza Stark Gene: atp6v0a2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5586 ATP6V0A2 Zornitza Stark Phenotypes for gene: ATP6V0A2 were changed from to Cutis laxa, autosomal recessive, type IIA, MIM# 219200; Wrinkly skin syndrome, MIM#278250
Intellectual disability syndromic and non-syndromic v0.5585 ATP6V0A2 Zornitza Stark Mode of inheritance for gene: ATP6V0A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5584 ATP6V0A2 Zornitza Stark reviewed gene: ATP6V0A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cutis laxa, autosomal recessive, type IIA, MIM# 219200, Wrinkly skin syndrome, MIM#278250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5584 ATR Zornitza Stark Marked gene: ATR as ready
Intellectual disability syndromic and non-syndromic v0.5584 ATR Zornitza Stark Gene: atr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5584 ATR Zornitza Stark Phenotypes for gene: ATR were changed from to Seckel syndrome 1, MIM# 210600
Intellectual disability syndromic and non-syndromic v0.5583 ATR Zornitza Stark Mode of inheritance for gene: ATR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5582 ATR Zornitza Stark reviewed gene: ATR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Seckel syndrome 1, MIM# 210600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5582 ATP6V1B2 Zornitza Stark Marked gene: ATP6V1B2 as ready
Intellectual disability syndromic and non-syndromic v0.5582 ATP6V1B2 Zornitza Stark Gene: atp6v1b2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5582 ATP6V1B2 Zornitza Stark Phenotypes for gene: ATP6V1B2 were changed from to Zimmermann-Laband syndrome 2, MIM# 616455
Intellectual disability syndromic and non-syndromic v0.5581 ATP6V1B2 Zornitza Stark Mode of inheritance for gene: ATP6V1B2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5580 ATP6V1B2 Zornitza Stark reviewed gene: ATP6V1B2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Zimmermann-Laband syndrome 2, MIM# 616455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5580 ATP6AP2 Zornitza Stark Marked gene: ATP6AP2 as ready
Intellectual disability syndromic and non-syndromic v0.5580 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5580 ATP6AP2 Zornitza Stark Phenotypes for gene: ATP6AP2 were changed from to Congenital disorder of glycosylation, type IIr MIM#301045 Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423
Intellectual disability syndromic and non-syndromic v0.5579 ATP6AP2 Zornitza Stark Mode of inheritance for gene: ATP6AP2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5578 ATP6AP2 Zornitza Stark commented on gene: ATP6AP2: These two conditions likely represent a spectrum of severity for a single disorder. ID is a feature of both.
Intellectual disability syndromic and non-syndromic v0.5578 ATP6AP2 Zornitza Stark reviewed gene: ATP6AP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type IIr MIM#301045 Intellectual developmental disorder, X-linked, syndromic, Hedera type MIM#300423; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5578 KCNH5 Zornitza Stark Phenotypes for gene: KCNH5 were changed from Neurodevelopmental disorder MONDO#0700092, KCNH5-related to Developmental and epileptic encephalopathy 112, MIM# 620537
Intellectual disability syndromic and non-syndromic v0.5577 KCNH5 Zornitza Stark Publications for gene: KCNH5 were set to https://www.medrxiv.org/content/10.1101/2022.04.26.22274147v1
Intellectual disability syndromic and non-syndromic v0.5576 KCNH5 Zornitza Stark reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: None; Publications: 36307226; Phenotypes: Developmental and epileptic encephalopathy 112, MIM# 620537; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5576 U2AF2 Zornitza Stark Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Developmental delay, dysmorphic facies, and brain anomalies, MIM# 620535
Intellectual disability syndromic and non-syndromic v0.5575 ETS1 Zornitza Stark Phenotypes for gene: ETS1 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, ETS1-related
Intellectual disability syndromic and non-syndromic v0.5574 ETS1 Zornitza Stark edited their review of gene: ETS1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, ETS1-related
Intellectual disability syndromic and non-syndromic v0.5574 EPHA7 Zornitza Stark Phenotypes for gene: EPHA7 were changed from Intellectual disability to Neurodevelopmental disorder MONDO:0700092,EPHA7-related
Intellectual disability syndromic and non-syndromic v0.5573 EPHA7 Zornitza Stark edited their review of gene: EPHA7: Changed phenotypes: Neurodevelopmental disorder MONDO:0700092,EPHA7-related
Intellectual disability syndromic and non-syndromic v0.5573 ELMOD1 Zornitza Stark Phenotypes for gene: ELMOD1 were changed from Intellectual disability to Neurodevelopmental disorder MONDO:0700092,ELMOD1-related
Intellectual disability syndromic and non-syndromic v0.5572 ELMOD1 Zornitza Stark edited their review of gene: ELMOD1: Changed phenotypes: Neurodevelopmental disorder MONDO:0700092,ELMOD1-related
Intellectual disability syndromic and non-syndromic v0.5572 EEF1D Zornitza Stark Phenotypes for gene: EEF1D were changed from Intellectual disability to Neurodevelopmental disorder MONDO:0700092, EEF1D-related
Intellectual disability syndromic and non-syndromic v0.5571 EEF1D Zornitza Stark edited their review of gene: EEF1D: Changed phenotypes: Neurodevelopmental disorder MONDO:0700092, EEF1D-related
Intellectual disability syndromic and non-syndromic v0.5571 DSCR3 Zornitza Stark Phenotypes for gene: DSCR3 were changed from Intellectual disability, no OMIM # yet to Neurodevelopmental disorder (MONDO:0700092), DSCR3-related
Intellectual disability syndromic and non-syndromic v0.5570 ATP13A2 Zornitza Stark Marked gene: ATP13A2 as ready
Intellectual disability syndromic and non-syndromic v0.5570 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5570 ATP13A2 Zornitza Stark Phenotypes for gene: ATP13A2 were changed from to Kufor-Rakeb syndrome, MIM# 606693
Intellectual disability syndromic and non-syndromic v0.5569 ATP13A2 Zornitza Stark Mode of inheritance for gene: ATP13A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5568 ATP13A2 Zornitza Stark Classified gene: ATP13A2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5568 ATP13A2 Zornitza Stark Gene: atp13a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5567 ATP13A2 Zornitza Stark reviewed gene: ATP13A2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Kufor-Rakeb syndrome, MIM# 606693; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5567 BRAF Zornitza Stark Marked gene: BRAF as ready
Intellectual disability syndromic and non-syndromic v0.5567 BRAF Zornitza Stark Gene: braf has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5567 BRAF Zornitza Stark Phenotypes for gene: BRAF were changed from to Cardiofaciocutaneous syndrome (MIM# 115150); Noonan syndrome (MIM# 613706); LEOPARD syndrome (MIM# 613707)
Intellectual disability syndromic and non-syndromic v0.5566 BRAF Zornitza Stark Publications for gene: BRAF were set to
Intellectual disability syndromic and non-syndromic v0.5565 BRAF Zornitza Stark Mode of pathogenicity for gene: BRAF was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.5564 BRAF Zornitza Stark Mode of inheritance for gene: BRAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5563 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Intellectual disability syndromic and non-syndromic v0.5563 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5563 SMARCA4 Zornitza Stark Phenotypes for gene: SMARCA4 were changed from to Coffin-Siris syndrome 4 (MIM# 614609)
Intellectual disability syndromic and non-syndromic v0.5562 SMARCA4 Zornitza Stark Publications for gene: SMARCA4 were set to
Intellectual disability syndromic and non-syndromic v0.5561 SMARCA4 Zornitza Stark Mode of pathogenicity for gene: SMARCA4 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.5560 SMARCA4 Zornitza Stark Mode of inheritance for gene: SMARCA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5559 SMC3 Zornitza Stark Marked gene: SMC3 as ready
Intellectual disability syndromic and non-syndromic v0.5559 SMC3 Zornitza Stark Gene: smc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5559 SMC3 Zornitza Stark Phenotypes for gene: SMC3 were changed from to Cornelia de Lange syndrome 3 MONDO:0012555
Intellectual disability syndromic and non-syndromic v0.5558 SMC3 Zornitza Stark Publications for gene: SMC3 were set to
Intellectual disability syndromic and non-syndromic v0.5557 SMC3 Zornitza Stark Mode of inheritance for gene: SMC3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5556 SMC1A Zornitza Stark Marked gene: SMC1A as ready
Intellectual disability syndromic and non-syndromic v0.5556 SMC1A Zornitza Stark Gene: smc1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5556 SMC1A Zornitza Stark Phenotypes for gene: SMC1A were changed from to Cornelia de Lange syndrome 2 MONDO:0010370
Intellectual disability syndromic and non-syndromic v0.5555 SMC1A Zornitza Stark Publications for gene: SMC1A were set to
Intellectual disability syndromic and non-syndromic v0.5554 SMC1A Zornitza Stark Mode of inheritance for gene: SMC1A was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5553 SMARCB1 Zornitza Stark Marked gene: SMARCB1 as ready
Intellectual disability syndromic and non-syndromic v0.5553 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5553 SMARCB1 Zornitza Stark Phenotypes for gene: SMARCB1 were changed from to Coffin-Siris syndrome 3 (MIM# 614608); MONDO:0015452
Intellectual disability syndromic and non-syndromic v0.5552 SMARCB1 Zornitza Stark Publications for gene: SMARCB1 were set to
Intellectual disability syndromic and non-syndromic v0.5551 SMARCB1 Zornitza Stark Mode of pathogenicity for gene: SMARCB1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.5550 SMARCB1 Zornitza Stark Mode of inheritance for gene: SMARCB1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 SMARCB1 Kaitlyn Dianna Weldon reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23556151; Phenotypes: Coffin-Siris syndrome MONDO:0015452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 SMC1A Kaitlyn Dianna Weldon reviewed gene: SMC1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301283; Phenotypes: Cornelia de Lange syndrome 2 MONDO:0010370; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5549 SMC3 Kaitlyn Dianna Weldon reviewed gene: SMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301283; Phenotypes: Cornelia de Lange syndrome 3 MONDO:0012555; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 SMARCB1 Claire Fryer-Smith reviewed gene: SMARCB1: 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: 22426308, 29907796, 3175698; Phenotypes: Coffin-Siris syndrome 3 (MIM# 614608); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 SMARCA4 Claire Fryer-Smith changed review comment from: Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges.

Missense and an in-frame deletion in SCARCA4 have been observed across 15 CSS patients in the literature (22426308, 23637025, 23929686), suggesting a dominant negative GoF effect.

LoF variants in SMARCA4 result in Rhabdoid tumor predisposition syndrome, which does not exhibit ID.; to: Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges.

Missense and an in-frame deletion in SMARCA4 have been observed across 15 CSS patients in the literature (22426308, 23637025, 23929686), suggesting a dominant negative GoF effect.

LoF variants in SMARCA4 result in Rhabdoid tumor predisposition syndrome, which does not exhibit ID.
Intellectual disability syndromic and non-syndromic v0.5549 SMARCA4 Claire Fryer-Smith reviewed gene: SMARCA4: 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: 22426308, 23929686, 23637025; Phenotypes: Coffin-Siris syndrome 4 (MIM# 614609); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 BRAF Claire Fryer-Smith reviewed gene: BRAF: 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: 10610177, 16474404, 19206169; Phenotypes: Cardiofaciocutaneous syndrome (MIM# 115150), Noonan syndrome (MIM# 613706), LEOPARD syndrome (MIM# 613707); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5549 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Intellectual disability syndromic and non-syndromic v0.5549 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5549 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from to developmental and epileptic encephalopathy, 4 MONDO:0012812
Intellectual disability syndromic and non-syndromic v0.5548 STXBP1 Zornitza Stark Publications for gene: STXBP1 were set to
Intellectual disability syndromic and non-syndromic v0.5547 STXBP1 Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5546 FH Zornitza Stark Marked gene: FH as ready
Intellectual disability syndromic and non-syndromic v0.5546 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5546 FH Zornitza Stark Phenotypes for gene: FH were changed from to Fumarase deficiency (MIM# 606812)
Intellectual disability syndromic and non-syndromic v0.5545 FH Zornitza Stark Publications for gene: FH were set to
Intellectual disability syndromic and non-syndromic v0.5544 FH Zornitza Stark Mode of inheritance for gene: FH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5543 TMEM70 Zornitza Stark Marked gene: TMEM70 as ready
Intellectual disability syndromic and non-syndromic v0.5543 TMEM70 Zornitza Stark Gene: tmem70 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5543 TMEM70 Zornitza Stark Phenotypes for gene: TMEM70 were changed from to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MIM# 614052
Intellectual disability syndromic and non-syndromic v0.5542 TMEM70 Zornitza Stark Publications for gene: TMEM70 were set to
Intellectual disability syndromic and non-syndromic v0.5541 FH Claire Fryer-Smith reviewed gene: FH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31746132, 29052812, 21560188; Phenotypes: Fumarase deficiency (MIM# 606812); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5541 TMEM70 Zornitza Stark Mode of inheritance for gene: TMEM70 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5540 TMEM70 Zornitza Stark reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, MIM# 614052; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5540 TMEM240 Zornitza Stark Marked gene: TMEM240 as ready
Intellectual disability syndromic and non-syndromic v0.5540 TMEM240 Zornitza Stark Gene: tmem240 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5540 TMEM240 Zornitza Stark Publications for gene: TMEM240 were set to
Intellectual disability syndromic and non-syndromic v0.5539 TMEM240 Zornitza Stark Phenotypes for gene: TMEM240 were changed from to Spinocerebellar ataxia 21, MIM# 607454; spinocerebellar ataxia type 21 MONDO:0011833
Intellectual disability syndromic and non-syndromic v0.5538 TMEM240 Zornitza Stark Mode of inheritance for gene: TMEM240 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5537 TMEM216 Zornitza Stark Marked gene: TMEM216 as ready
Intellectual disability syndromic and non-syndromic v0.5537 TMEM216 Zornitza Stark Gene: tmem216 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5537 TMEM216 Zornitza Stark Phenotypes for gene: TMEM216 were changed from to Joubert syndrome 2 MONDO:0011963
Intellectual disability syndromic and non-syndromic v0.5536 TMEM216 Zornitza Stark Publications for gene: TMEM216 were set to
Intellectual disability syndromic and non-syndromic v0.5535 TMEM216 Zornitza Stark Mode of inheritance for gene: TMEM216 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5534 TMCO1 Zornitza Stark Marked gene: TMCO1 as ready
Intellectual disability syndromic and non-syndromic v0.5534 TMCO1 Zornitza Stark Gene: tmco1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5534 TMCO1 Zornitza Stark Phenotypes for gene: TMCO1 were changed from to Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1, MIM# 213980; cerebrofaciothoracic dysplasia MONDO:0008952
Intellectual disability syndromic and non-syndromic v0.5533 TMCO1 Zornitza Stark Publications for gene: TMCO1 were set to
Intellectual disability syndromic and non-syndromic v0.5532 TMCO1 Zornitza Stark Mode of inheritance for gene: TMCO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5531 TCF4 Zornitza Stark Marked gene: TCF4 as ready
Intellectual disability syndromic and non-syndromic v0.5531 TCF4 Zornitza Stark Gene: tcf4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5531 TCF4 Zornitza Stark Phenotypes for gene: TCF4 were changed from to Pitt-Hopkins syndrome MONDO:0012589
Intellectual disability syndromic and non-syndromic v0.5530 TCF4 Zornitza Stark Publications for gene: TCF4 were set to
Intellectual disability syndromic and non-syndromic v0.5529 TCF4 Zornitza Stark Mode of inheritance for gene: TCF4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5528 STRA6 Kaitlyn Dianna Weldon reviewed gene: STRA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273977; Phenotypes: Matthew-Wood syndrome MONDO:0011010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5528 TBC1D24 Zornitza Stark Marked gene: TBC1D24 as ready
Intellectual disability syndromic and non-syndromic v0.5528 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5528 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from to Developmental and epileptic encephalopathy 16, MIM# 615338; DOORS syndrome, MIM# 220500
Intellectual disability syndromic and non-syndromic v0.5527 TBC1D24 Zornitza Stark Publications for gene: TBC1D24 were set to
Intellectual disability syndromic and non-syndromic v0.5526 TBC1D24 Zornitza Stark Mode of inheritance for gene: TBC1D24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5525 TAZ Zornitza Stark Marked gene: TAZ as ready
Intellectual disability syndromic and non-syndromic v0.5525 TAZ Zornitza Stark Gene: taz has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5525 TAZ Zornitza Stark Phenotypes for gene: TAZ were changed from to Barth syndrome MONDO:0010543
Intellectual disability syndromic and non-syndromic v0.5524 STXBP1 Kaitlyn Dianna Weldon reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27905812; Phenotypes: developmental and epileptic encephalopathy, 4 MONDO:0012812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5524 TAZ Zornitza Stark Publications for gene: TAZ were set to
Intellectual disability syndromic and non-syndromic v0.5523 TAZ Zornitza Stark Mode of inheritance for gene: TAZ was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5522 TAT Zornitza Stark Marked gene: TAT as ready
Intellectual disability syndromic and non-syndromic v0.5522 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5522 TAT Zornitza Stark Phenotypes for gene: TAT were changed from to tyrosinemia type II MONDO:0010160
Intellectual disability syndromic and non-syndromic v0.5521 TAT Zornitza Stark Publications for gene: TAT were set to
Intellectual disability syndromic and non-syndromic v0.5520 TAT Zornitza Stark Mode of inheritance for gene: TAT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5519 TANGO2 Zornitza Stark Marked gene: TANGO2 as ready
Intellectual disability syndromic and non-syndromic v0.5519 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5519 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878; metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MONDO:0014812
Intellectual disability syndromic and non-syndromic v0.5518 TANGO2 Zornitza Stark Publications for gene: TANGO2 were set to
Intellectual disability syndromic and non-syndromic v0.5517 TANGO2 Zornitza Stark Mode of inheritance for gene: TANGO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5516 NF1 Claire Fryer-Smith changed review comment from: NF1 shows a high degree of phenotypic variability. Intellectual disability has been shown to occur in 4%-8% of cases, typically appearing in childhood and persisting through life (PMID: 23931823, 10762507).; to: NF1 shows a high degree of phenotypic variability. Intellectual disability has been shown to occur in 4%-8% of cases, typically appearing in childhood and persisting through life (PMID: 23931823, 10762507).
Intellectual disability syndromic and non-syndromic v0.5516 NF1 Claire Fryer-Smith reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23931823, 10762507; Phenotypes: Neurofibromatosis, type 1 (MIM#162200); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5516 SUOX Kaitlyn Dianna Weldon reviewed gene: SUOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 28933809; Phenotypes: isolated sulfite oxidase deficiency MONDO:0010089; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5516 SYN1 Zornitza Stark Marked gene: SYN1 as ready
Intellectual disability syndromic and non-syndromic v0.5516 SYN1 Zornitza Stark Gene: syn1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5516 SYN1 Zornitza Stark Phenotypes for gene: SYN1 were changed from to X-linked complex neurodevelopmental disorder MONDO:0100148; epilepsy, X-linked 1, with variable learning disabilities and behavior disorders MONDO:0010339
Intellectual disability syndromic and non-syndromic v0.5515 SYN1 Zornitza Stark Mode of inheritance for gene: SYN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5514 SYN1 Kaitlyn Dianna Weldon reviewed gene: SYN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders MONDO:0010339; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5514 MYCN Naomi Baker commented on gene: MYCN: Three individuals now reported with gain-of-function missense variants (identical variant in two individuals). 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.
Intellectual disability syndromic and non-syndromic v0.5514 MAST4 Ain Roesley Classified gene: MAST4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5514 MAST4 Ain Roesley Gene: mast4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5514 MAST4 Ain Roesley Classified gene: MAST4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5514 MAST4 Ain Roesley Gene: mast4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5513 MYCN Naomi Baker reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:37710961; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), MYCN-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5513 MAST4 Ain Roesley Marked gene: MAST4 as ready
Intellectual disability syndromic and non-syndromic v0.5513 MAST4 Ain Roesley Gene: mast4 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5513 ATP2B2 Zornitza Stark Marked gene: ATP2B2 as ready
Intellectual disability syndromic and non-syndromic v0.5513 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5513 ATP2B2 Zornitza Stark Classified gene: ATP2B2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5513 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5512 MAST4 Ain Roesley gene: MAST4 was added
gene: MAST4 was added to Intellectual disability syndromic and non-syndromic. 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
Penetrance for gene: MAST4 were set to Complete
Review for gene: MAST4 was set to GREEN
gene: MAST4 was marked as current diagnostic
Added comment: PMID: 36910266 - 4 families with 4 affecteds, 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 syndromic and non-syndromic v0.5511 COG3 Zornitza Stark Marked gene: COG3 as ready
Intellectual disability syndromic and non-syndromic v0.5511 COG3 Zornitza Stark Gene: cog3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5511 COG3 Zornitza Stark Classified gene: COG3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5511 COG3 Zornitza Stark Gene: cog3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5510 ZBTB47 Elena Savva Classified gene: ZBTB47 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5510 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5510 ZBTB47 Elena Savva Classified gene: ZBTB47 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5510 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5509 ZBTB47 Elena Savva Marked gene: ZBTB47 as ready
Intellectual disability syndromic and non-syndromic v0.5509 ZBTB47 Elena Savva Gene: zbtb47 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5509 ATP2B2 Andrew Fennell gene: ATP2B2 was added
gene: ATP2B2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B2 were set to PMID: 37675773
Phenotypes for gene: ATP2B2 were set to Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related
Mode of pathogenicity for gene: ATP2B2 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: ATP2B2 was set to GREEN
Added comment: 7 unrelated individuals reported with a variable phenotype including dystonia, ataxia, intellectual disability, behavioural symptoms, and seizures.

All patients have either missense variants or frameshift variants in the penultimate exon not expected to lead to NMD. This is in contrast to patients with isolated deafness previously reported to have nonsense, frameshift, or splice-site variants outside of this region.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5509 COG3 Daniel Flanagan gene: COG3 was added
gene: COG3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to PMID: 37711075
Phenotypes for gene: COG3 were set to Neurodevelopmental disorder (MONDO#0700092), COG3-related
Review for gene: COG3 was set to AMBER
Added comment: Two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5509 ZBTB47 Elena Savva gene: ZBTB47 was added
gene: ZBTB47 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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 patients with de novo missense, 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
- Minimal PTCs in gnomAD
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5508 TANGO2 Kaitlyn Dianna Weldon reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29369572; Phenotypes: obsolete metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MONDO:0014812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TAT Kaitlyn Dianna Weldon reviewed gene: TAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 28255985; Phenotypes: tyrosinemia type II MONDO:0010160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TAZ Kaitlyn Dianna Weldon reviewed gene: TAZ: Rating: GREEN; Mode of pathogenicity: None; Publications: 25299040; Phenotypes: Barth syndrome MONDO:0010543; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5508 TBC1D24 Kaitlyn Dianna Weldon reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: None; Publications: 25719194; Phenotypes: familial infantile myoclonic epilepsy MONDO:0011506, DOORS syndrome MONDO:0009079; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TCF4 Kaitlyn Dianna Weldon reviewed gene: TCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22934316; Phenotypes: Pitt-Hopkins syndrome MONDO:0012589; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5508 TMCO1 Kaitlyn Dianna Weldon reviewed gene: TMCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 1204988, 1640432, 15326640, 20018682; Phenotypes: obsolete cerebrofaciothoracic dysplasia MONDO:0008952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TMEM216 Kaitlyn Dianna Weldon reviewed gene: TMEM216: Rating: GREEN; Mode of pathogenicity: None; Publications: 20036350; Phenotypes: Joubert syndrome 2 MONDO:0011963; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 TMEM240 Kaitlyn Dianna Weldon reviewed gene: TMEM240: Rating: GREEN; Mode of pathogenicity: None; Publications: 25070513; Phenotypes: spinocerebellar ataxia type 21 MONDO:0011833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5508 TMEM70 Kaitlyn Dianna Weldon reviewed gene: TMEM70: Rating: GREEN; Mode of pathogenicity: None; Publications: 18953340; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5508 ATRX Zornitza Stark Marked gene: ATRX as ready
Intellectual disability syndromic and non-syndromic v0.5508 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5508 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from to ATR-X-related syndrome MONDO:0016980
Intellectual disability syndromic and non-syndromic v0.5507 ATRX Zornitza Stark Mode of inheritance for gene: ATRX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5506 ATRX Zornitza Stark reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ATR-X-related syndrome MONDO:0016980; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5506 DHX32 Zornitza Stark Phenotypes for gene: DHX32 were changed from Intellectual disability, spastic diplegia, dystonia, brain abnormalities to Neurodevelopmental disorder, MONDO:0700092, DHX32-related
Intellectual disability syndromic and non-syndromic v0.5505 DDX23 Zornitza Stark Phenotypes for gene: DDX23 were changed from DDX23-associated neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, DDX23-related
Intellectual disability syndromic and non-syndromic v0.5504 DDX23 Zornitza Stark edited their review of gene: DDX23: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, DDX23-related
Intellectual disability syndromic and non-syndromic v0.5504 CSNK1G1 Zornitza Stark Phenotypes for gene: CSNK1G1 were changed from Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of the face; Abnromality of limbs to Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related
Intellectual disability syndromic and non-syndromic v0.5503 CTNND2 Zornitza Stark Phenotypes for gene: CTNND2 were changed from Intellectual disability; Autism; Epilepsy to Neurodevelopmental disorder, MONDO:0700092, CTNND2-related
Intellectual disability syndromic and non-syndromic v0.5502 CSDE1 Zornitza Stark Phenotypes for gene: CSDE1 were changed from Autism; intellectual disability; seizures; macrocephaly to Neurodevelopmental disorder, MONDO:0700092, CSDE1-related
Intellectual disability syndromic and non-syndromic v0.5501 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Intellectual disability syndromic and non-syndromic v0.5501 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5501 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from to pontocerebellar hypoplasia type 2A MONDO:0010190
Intellectual disability syndromic and non-syndromic v0.5500 TSEN54 Zornitza Stark Publications for gene: TSEN54 were set to
Intellectual disability syndromic and non-syndromic v0.5499 TSEN54 Zornitza Stark Mode of inheritance for gene: TSEN54 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5498 TSFM Zornitza Stark Marked gene: TSFM as ready
Intellectual disability syndromic and non-syndromic v0.5498 TSFM Zornitza Stark Gene: tsfm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5498 TSFM Zornitza Stark Phenotypes for gene: TSFM were changed from to Combined oxidative phosphorylation deficiency 3, MIM#610505
Intellectual disability syndromic and non-syndromic v0.5497 TSFM Zornitza Stark Publications for gene: TSFM were set to
Intellectual disability syndromic and non-syndromic v0.5496 TSFM Zornitza Stark Mode of inheritance for gene: TSFM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5495 TSFM Zornitza Stark reviewed gene: TSFM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 3, MIM#610505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5495 TSHB Zornitza Stark Marked gene: TSHB as ready
Intellectual disability syndromic and non-syndromic v0.5495 TSHB Zornitza Stark Gene: tshb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5495 TSHB Zornitza Stark Phenotypes for gene: TSHB were changed from to Central congenital hypothyroidism Orphanet:226298
Intellectual disability syndromic and non-syndromic v0.5494 TSHB Zornitza Stark Publications for gene: TSHB were set to
Intellectual disability syndromic and non-syndromic v0.5493 TSHB Zornitza Stark Mode of inheritance for gene: TSHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5492 TSHB Zornitza Stark reviewed gene: TSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Central congenital hypothyroidism Orphanet:226298; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5492 SNAPC4 Zornitza Stark Phenotypes for gene: SNAPC4 were changed from Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related to Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction, MIM# 620515
Intellectual disability syndromic and non-syndromic v0.5491 TSEN54 Kaitlyn Dianna Weldon reviewed gene: TSEN54: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301773; Phenotypes: pontocerebellar hypoplasia type 2A MONDO:0010190; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5491 TSFM Kaitlyn Dianna Weldon reviewed gene: TSFM: Rating: GREEN; Mode of pathogenicity: None; Publications: 25037205, 33816677, 31451716, 22499341; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5491 TSHB Kaitlyn Dianna Weldon reviewed gene: TSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 15292359, 27362444; Phenotypes: Central congenital hypothyroidism Orphanet:226298; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5491 CNTN6 Zornitza Stark Phenotypes for gene: CNTN6 were changed from Intellectual disability; autism; Tourette syndrome; schizophrenia to Neurodevelopmental disorder, MONDO:0700092, CNTN6-related
Intellectual disability syndromic and non-syndromic v0.5490 CNTN6 Zornitza Stark edited their review of gene: CNTN6: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CNTN6-related
Intellectual disability syndromic and non-syndromic v0.5490 CNTN3 Zornitza Stark Phenotypes for gene: CNTN3 were changed from to Neurodevelopmental disorder, MONDO:0700092, CNTN3-related
Intellectual disability syndromic and non-syndromic v0.5489 CNTN3 Zornitza Stark edited their review of gene: CNTN3: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CNTN3-related
Intellectual disability syndromic and non-syndromic v0.5489 CNKSR1 Zornitza Stark Phenotypes for gene: CNKSR1 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CNKSR1-related
Intellectual disability syndromic and non-syndromic v0.5488 CMAS Zornitza Stark Phenotypes for gene: CMAS were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, CMAS-related
Intellectual disability syndromic and non-syndromic v0.5487 CMAS Zornitza Stark edited their review of gene: CMAS: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, CMAS-related
Intellectual disability syndromic and non-syndromic v0.5487 TTC37 Zornitza Stark Marked gene: TTC37 as ready
Intellectual disability syndromic and non-syndromic v0.5487 TTC37 Zornitza Stark Gene: ttc37 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5487 TTC37 Zornitza Stark Phenotypes for gene: TTC37 were changed from to trichohepatoenteric syndrome 1 MONDO:0024541
Intellectual disability syndromic and non-syndromic v0.5486 TTC37 Zornitza Stark Publications for gene: TTC37 were set to
Intellectual disability syndromic and non-syndromic v0.5485 TTC37 Zornitza Stark Mode of inheritance for gene: TTC37 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5484 TTC37 Zornitza Stark Mode of inheritance for gene: TTC37 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5484 NCKAP1 Ain Roesley Phenotypes for gene: NCKAP1 were changed from Neurodevelopmental disorder (MONDO#0700092)​​​​​​​, NCKAP1-related to Neurodevelopmental disorder (MONDO#0700092)​​​​​​​, NCKAP1-related
Intellectual disability syndromic and non-syndromic v0.5483 NCKAP1 Ain Roesley Phenotypes for gene: NCKAP1 were changed from Intellectual disability; autism to Neurodevelopmental disorder (MONDO#0700092)​​​​​​​, NCKAP1-related
Intellectual disability syndromic and non-syndromic v0.5482 BLOC1S1 Zornitza Stark Phenotypes for gene: BLOC1S1 were changed from severe intellectual disability; severe global developmental delay; epilepsy to Neurodevelopmental disorder, MONDO:0700092, BLOC1S1-related
Intellectual disability syndromic and non-syndromic v0.5481 BLOC1S1 Zornitza Stark edited their review of gene: BLOC1S1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, BLOC1S1-related
Intellectual disability syndromic and non-syndromic v0.5481 ASTN2 Zornitza Stark Marked gene: ASTN2 as ready
Intellectual disability syndromic and non-syndromic v0.5481 ASTN2 Zornitza Stark Gene: astn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5481 ASTN2 Zornitza Stark Classified gene: ASTN2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5481 ASTN2 Zornitza Stark Gene: astn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5480 ASTN2 Zornitza Stark gene: ASTN2 was added
gene: ASTN2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ASTN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ASTN2 were set to 28940097; 34412080; 27138430
Phenotypes for gene: ASTN2 were set to Neurodevelopmental disorder, MONDO:0700092, ASTN2-related
Review for gene: ASTN2 was set to AMBER
Added comment: Candidate gene reported by Anazi et al; rare CNVs also reported; other circumstantial evidence.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5479 TTC37 Kaitlyn Dianna Weldon reviewed gene: TTC37: Rating: GREEN; Mode of pathogenicity: None; Publications: 29334452; Phenotypes: trichohepatoenteric syndrome 1 MONDO:0024541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5479 MCCC1 Bryony Thompson Marked gene: MCCC1 as ready
Intellectual disability syndromic and non-syndromic v0.5479 MCCC1 Bryony Thompson Gene: mccc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5479 MCCC1 Bryony Thompson Phenotypes for gene: MCCC1 were changed from to 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200; Organic acidurias
Intellectual disability syndromic and non-syndromic v0.5478 MCCC1 Bryony Thompson Publications for gene: MCCC1 were set to
Intellectual disability syndromic and non-syndromic v0.5477 MCCC1 Bryony Thompson Mode of inheritance for gene: MCCC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5476 MCCC1 Bryony Thompson Classified gene: MCCC1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5476 MCCC1 Bryony Thompson Gene: mccc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5475 MCCC1 Bryony Thompson reviewed gene: MCCC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 36822454, 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency MIM#210200, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5475 AKAP6 Zornitza Stark Phenotypes for gene: AKAP6 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, AKAP6-related
Intellectual disability syndromic and non-syndromic v0.5474 AKAP6 Zornitza Stark edited their review of gene: AKAP6: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, AKAP6-related
Intellectual disability syndromic and non-syndromic v0.5474 AGMO Zornitza Stark Phenotypes for gene: AGMO were changed from microcephaly; intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, AGMO-related
Intellectual disability syndromic and non-syndromic v0.5473 ACTL6A Zornitza Stark Phenotypes for gene: ACTL6A were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092, ACTL6A-related
Intellectual disability syndromic and non-syndromic v0.5472 ACTL6A Zornitza Stark edited their review of gene: ACTL6A: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, ACTL6A-related
Intellectual disability syndromic and non-syndromic v0.5472 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Intellectual disability syndromic and non-syndromic v0.5472 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5472 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from to complex cortical dysplasia with other brain malformations 1 MONDO:0013541
Intellectual disability syndromic and non-syndromic v0.5471 TUBB3 Zornitza Stark Publications for gene: TUBB3 were set to
Intellectual disability syndromic and non-syndromic v0.5470 TUBB3 Zornitza Stark Mode of inheritance for gene: TUBB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5469 TUBB4A Zornitza Stark Marked gene: TUBB4A as ready
Intellectual disability syndromic and non-syndromic v0.5469 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5469 TUBB4A Zornitza Stark Phenotypes for gene: TUBB4A were changed from to hypomyelinating leukodystrophy 6 MONDO:0012905
Intellectual disability syndromic and non-syndromic v0.5468 TUBB4A Zornitza Stark Publications for gene: TUBB4A were set to
Intellectual disability syndromic and non-syndromic v0.5467 TUBB4A Zornitza Stark Mode of inheritance for gene: TUBB4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5466 TH Zornitza Stark Marked gene: TH as ready
Intellectual disability syndromic and non-syndromic v0.5466 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5466 TH Zornitza Stark Phenotypes for gene: TH were changed from to Segawa syndrome, recessive MIM#605407
Intellectual disability syndromic and non-syndromic v0.5465 TH Zornitza Stark Publications for gene: TH were set to
Intellectual disability syndromic and non-syndromic v0.5464 TH Zornitza Stark Mode of inheritance for gene: TH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5463 TH Zornitza Stark Tag treatable tag was added to gene: TH.
Intellectual disability syndromic and non-syndromic v0.5463 PTEN Zornitza Stark Marked gene: PTEN as ready
Intellectual disability syndromic and non-syndromic v0.5463 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5463 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from to Cowden syndrome 1 MIM#158350; Macrocephaly/autism syndrome MIM#605309
Intellectual disability syndromic and non-syndromic v0.5462 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5461 TUBG1 Zornitza Stark Marked gene: TUBG1 as ready
Intellectual disability syndromic and non-syndromic v0.5461 TUBG1 Zornitza Stark Gene: tubg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5461 TUBG1 Zornitza Stark Phenotypes for gene: TUBG1 were changed from to complex cortical dysplasia with other brain malformations 4 MONDO:0014171
Intellectual disability syndromic and non-syndromic v0.5460 TUBG1 Zornitza Stark Publications for gene: TUBG1 were set to
Intellectual disability syndromic and non-syndromic v0.5459 TUBG1 Zornitza Stark Mode of inheritance for gene: TUBG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5458 TWIST1 Zornitza Stark Marked gene: TWIST1 as ready
Intellectual disability syndromic and non-syndromic v0.5458 TWIST1 Zornitza Stark Gene: twist1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5458 TWIST1 Zornitza Stark Phenotypes for gene: TWIST1 were changed from to Saethre-Chotzen syndrome MONDO:0007042
Intellectual disability syndromic and non-syndromic v0.5457 TWIST1 Zornitza Stark Publications for gene: TWIST1 were set to
Intellectual disability syndromic and non-syndromic v0.5456 TWIST1 Zornitza Stark Mode of inheritance for gene: TWIST1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5455 UBA5 Zornitza Stark Marked gene: UBA5 as ready
Intellectual disability syndromic and non-syndromic v0.5455 UBA5 Zornitza Stark Gene: uba5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5455 UBA5 Zornitza Stark Phenotypes for gene: UBA5 were changed from to Epileptic encephalopathy, early infantile, 44 (MIM#617132)
Intellectual disability syndromic and non-syndromic v0.5454 UBA5 Zornitza Stark Publications for gene: UBA5 were set to 33811063
Intellectual disability syndromic and non-syndromic v0.5453 UBA5 Zornitza Stark Publications for gene: UBA5 were set to
Intellectual disability syndromic and non-syndromic v0.5452 UBA5 Zornitza Stark Mode of inheritance for gene: UBA5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5451 UBE3A Zornitza Stark Marked gene: UBE3A as ready
Intellectual disability syndromic and non-syndromic v0.5451 UBE3A Zornitza Stark Gene: ube3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5451 UBE3A Zornitza Stark Phenotypes for gene: UBE3A were changed from to Angelman syndrome MONDO:0007113
Intellectual disability syndromic and non-syndromic v0.5450 UBE3A Zornitza Stark Publications for gene: UBE3A were set to
Intellectual disability syndromic and non-syndromic v0.5449 UBE3A Zornitza Stark Mode of inheritance for gene: UBE3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Intellectual disability syndromic and non-syndromic v0.5448 SDHA Zornitza Stark Marked gene: SDHA as ready
Intellectual disability syndromic and non-syndromic v0.5448 SDHA Zornitza Stark Gene: sdha has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5448 SDHA Zornitza Stark Phenotypes for gene: SDHA were changed from to Mitochondrial complex II deficiency, nuclear type 1 MIM#252011
Intellectual disability syndromic and non-syndromic v0.5447 SDHA Zornitza Stark Publications for gene: SDHA were set to
Intellectual disability syndromic and non-syndromic v0.5446 SDHA Zornitza Stark Mode of inheritance for gene: SDHA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5445 VLDLR Zornitza Stark Marked gene: VLDLR as ready
Intellectual disability syndromic and non-syndromic v0.5445 VLDLR Zornitza Stark Gene: vldlr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5445 VLDLR Zornitza Stark Phenotypes for gene: VLDLR were changed from to cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 MONDO:0024542
Intellectual disability syndromic and non-syndromic v0.5444 VLDLR Zornitza Stark Publications for gene: VLDLR were set to
Intellectual disability syndromic and non-syndromic v0.5443 VLDLR Zornitza Stark Mode of inheritance for gene: VLDLR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5442 VPS13B Zornitza Stark Marked gene: VPS13B as ready
Intellectual disability syndromic and non-syndromic v0.5442 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5442 VPS13B Zornitza Stark Phenotypes for gene: VPS13B were changed from to Cohen syndrome MONDO:0008999
Intellectual disability syndromic and non-syndromic v0.5441 VPS13B Zornitza Stark Publications for gene: VPS13B were set to
Intellectual disability syndromic and non-syndromic v0.5440 VPS13B Zornitza Stark Mode of inheritance for gene: VPS13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5439 SCAF4 Zornitza Stark Phenotypes for gene: SCAF4 were changed from Mild intellectual disability; seizures; behavioral abnormalities to Fliedner-Zweier syndrome, MIM#620511
Intellectual disability syndromic and non-syndromic v0.5438 SCAF4 Zornitza Stark reviewed gene: SCAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fliedner-Zweier syndrome, MIM#620511; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5438 VRK1 Zornitza Stark Marked gene: VRK1 as ready
Intellectual disability syndromic and non-syndromic v0.5438 VRK1 Zornitza Stark Gene: vrk1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5438 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from to pontocerebellar hypoplasia type 1A MONDO:0011866
Intellectual disability syndromic and non-syndromic v0.5437 VRK1 Zornitza Stark Publications for gene: VRK1 were set to
Intellectual disability syndromic and non-syndromic v0.5436 VRK1 Zornitza Stark Mode of inheritance for gene: VRK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5435 WDR45 Zornitza Stark Marked gene: WDR45 as ready
Intellectual disability syndromic and non-syndromic v0.5435 WDR45 Zornitza Stark Gene: wdr45 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5435 WDR45 Zornitza Stark Phenotypes for gene: WDR45 were changed from to X-linked complex neurodevelopmental disorder MONDO:0100148; neurodegeneration with brain iron accumulation 5 MONDO:0010476
Intellectual disability syndromic and non-syndromic v0.5434 WDR45 Zornitza Stark Publications for gene: WDR45 were set to
Intellectual disability syndromic and non-syndromic v0.5433 WDR45 Zornitza Stark Mode of inheritance for gene: WDR45 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5432 WDR73 Zornitza Stark Marked gene: WDR73 as ready
Intellectual disability syndromic and non-syndromic v0.5432 WDR73 Zornitza Stark Gene: wdr73 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5432 WDR73 Zornitza Stark Phenotypes for gene: WDR73 were changed from to Galloway-Mowat syndrome 1 MONDO:0033005
Intellectual disability syndromic and non-syndromic v0.5431 WDR73 Zornitza Stark Publications for gene: WDR73 were set to
Intellectual disability syndromic and non-syndromic v0.5430 WDR73 Zornitza Stark Mode of inheritance for gene: WDR73 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5429 SMAD4 Zornitza Stark Marked gene: SMAD4 as ready
Intellectual disability syndromic and non-syndromic v0.5429 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5429 SMAD4 Zornitza Stark Phenotypes for gene: SMAD4 were changed from to Myhre syndrome MIM#139210
Intellectual disability syndromic and non-syndromic v0.5428 SMAD4 Zornitza Stark Publications for gene: SMAD4 were set to
Intellectual disability syndromic and non-syndromic v0.5427 SMAD4 Zornitza Stark Mode of inheritance for gene: SMAD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5426 WWOX Zornitza Stark Marked gene: WWOX as ready
Intellectual disability syndromic and non-syndromic v0.5426 WWOX Zornitza Stark Gene: wwox has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5426 WWOX Zornitza Stark Phenotypes for gene: WWOX were changed from to developmental and epileptic encephalopathy, 28 MONDO:0014533; autosomal recessive spinocerebellar ataxia 12 MONDO:0013687
Intellectual disability syndromic and non-syndromic v0.5425 WWOX Zornitza Stark Publications for gene: WWOX were set to
Intellectual disability syndromic and non-syndromic v0.5424 WWOX Zornitza Stark Mode of inheritance for gene: WWOX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5423 XRCC4 Zornitza Stark Marked gene: XRCC4 as ready
Intellectual disability syndromic and non-syndromic v0.5423 XRCC4 Zornitza Stark Gene: xrcc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5423 XRCC4 Zornitza Stark Phenotypes for gene: XRCC4 were changed from to Short stature, microcephaly, and endocrine dysfunction MIM#616541, MONDO:0014686
Intellectual disability syndromic and non-syndromic v0.5422 XRCC4 Zornitza Stark Publications for gene: XRCC4 were set to
Intellectual disability syndromic and non-syndromic v0.5421 XRCC4 Zornitza Stark Mode of inheritance for gene: XRCC4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5420 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Intellectual disability syndromic and non-syndromic v0.5420 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5420 TUBB2B Zornitza Stark Phenotypes for gene: TUBB2B were changed from to Cortical dysplasia, complex, with other brain malformations 7 MIM#610031
Intellectual disability syndromic and non-syndromic v0.5419 TUBB2B Zornitza Stark Publications for gene: TUBB2B were set to
Intellectual disability syndromic and non-syndromic v0.5418 TUBB2B Zornitza Stark Mode of inheritance for gene: TUBB2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5417 ZDHHC9 Zornitza Stark Marked gene: ZDHHC9 as ready
Intellectual disability syndromic and non-syndromic v0.5417 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5417 ZDHHC9 Zornitza Stark Phenotypes for gene: ZDHHC9 were changed from to Syndromic X-linked intellectual disability Raymond type MONDO:0010427
Intellectual disability syndromic and non-syndromic v0.5416 ZDHHC9 Zornitza Stark Publications for gene: ZDHHC9 were set to
Intellectual disability syndromic and non-syndromic v0.5415 ZDHHC9 Zornitza Stark Mode of inheritance for gene: ZDHHC9 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5414 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Intellectual disability syndromic and non-syndromic v0.5414 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5414 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from to Spastic paraplegia 15, autosomal recessive, MIM# 270700; hereditary spastic paraplegia 15, MONDO:0010044
Intellectual disability syndromic and non-syndromic v0.5413 ZFYVE26 Zornitza Stark Publications for gene: ZFYVE26 were set to
Intellectual disability syndromic and non-syndromic v0.5412 ZFYVE26 Zornitza Stark Mode of inheritance for gene: ZFYVE26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5411 ZIC2 Zornitza Stark Marked gene: ZIC2 as ready
Intellectual disability syndromic and non-syndromic v0.5411 ZIC2 Zornitza Stark Gene: zic2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5411 ZIC2 Zornitza Stark Phenotypes for gene: ZIC2 were changed from to Holoprosencephaly 5 MONDO:0012322
Intellectual disability syndromic and non-syndromic v0.5410 ZIC2 Zornitza Stark Publications for gene: ZIC2 were set to
Intellectual disability syndromic and non-syndromic v0.5409 ZIC2 Zornitza Stark Mode of inheritance for gene: ZIC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5408 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Intellectual disability syndromic and non-syndromic v0.5408 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5408 TSC1 Zornitza Stark Phenotypes for gene: TSC1 were changed from to Tuberous sclerosis MIM#191100
Intellectual disability syndromic and non-syndromic v0.5407 TSC1 Zornitza Stark Publications for gene: TSC1 were set to
Intellectual disability syndromic and non-syndromic v0.5406 TSC1 Zornitza Stark Mode of inheritance for gene: TSC1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5405 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Intellectual disability syndromic and non-syndromic v0.5405 TSC2 Zornitza Stark Gene: tsc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5405 TSC2 Zornitza Stark Phenotypes for gene: TSC2 were changed from to Tuberous sclerosis MIM#613254
Intellectual disability syndromic and non-syndromic v0.5404 TSC2 Zornitza Stark Publications for gene: TSC2 were set to
Intellectual disability syndromic and non-syndromic v0.5403 TSC2 Zornitza Stark Mode of inheritance for gene: TSC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5402 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Intellectual disability syndromic and non-syndromic v0.5402 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5402 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from mild intellectual disability; congenital heart disease; disorder of sexual differentiation; dysmorphic features to Syndromic disease, MONDO:0002254, NR2F2-related
Intellectual disability syndromic and non-syndromic v0.5401 NR2F2 Zornitza Stark Publications for gene: NR2F2 were set to 29478779; 29663647
Intellectual disability syndromic and non-syndromic v0.5400 NR2F2 Zornitza Stark Classified gene: NR2F2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5400 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5399 TUBB3 Kaitlyn Dianna Weldon reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20829227; Phenotypes: complex cortical dysplasia with other brain malformations 1 MONDO:0013541; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TUBB4A Kaitlyn Dianna Weldon reviewed gene: TUBB4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37529938, 35661708, 27538619, 24526230; Phenotypes: hypomyelinating leukodystrophy 6 MONDO:0012905, torsion dystonia 4 MONDO:0007493; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5399 TH Claire Fryer-Smith reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: 22815559, 11196107, 10585338; Phenotypes: Segawa syndrome, recessive MIM#605407; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 PTEN Claire Fryer-Smith reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21194675, 1859181, 23470840; Phenotypes: Cowden syndrome 1 MIM#158350, Lhermitte-Duclos disease MIM#158350, Macrocephaly/autism syndrome MIM#605309, Prostate cancer, somatic MIM#176807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TUBG1 Kaitlyn Dianna Weldon reviewed gene: TUBG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29706637, 23603762; Phenotypes: complex cortical dysplasia with other brain malformations 4 MONDO:0014171, lissencephaly spectrum disorders MONDO:0018838; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TWIST1 Kaitlyn Dianna Weldon reviewed gene: TWIST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301368; Phenotypes: Saethre-Chotzen syndrome MONDO:0007042; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 UBA5 Kaitlyn Dianna Weldon reviewed gene: UBA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33811063; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 UBE3A Kaitlyn Dianna Weldon reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301323; Phenotypes: Angelman syndrome MONDO:0007113; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Intellectual disability syndromic and non-syndromic v0.5399 SDHA Claire Fryer-Smith reviewed gene: SDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 1492653, 23322652; Phenotypes: Cardiomyopathy, dilated, 1GG MIM#613642, Mitochondrial complex II deficiency, nuclear type 1 MIM#252011, Neurodegeneration with ataxia and late-onset optic atrophy MIM#619259, Paragangliomas MIM#614165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 VLDLR Kaitlyn Dianna Weldon reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301729; Phenotypes: cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 MONDO:0024542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 VPS13B Kaitlyn Dianna Weldon reviewed gene: VPS13B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301655; Phenotypes: Cohen syndrome MONDO:0008999; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 VRK1 Kaitlyn Dianna Weldon reviewed gene: VRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19646678; Phenotypes: pontocerebellar hypoplasia type 1A MONDO:0011866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 WDR45 Kaitlyn Dianna Weldon reviewed gene: WDR45: Rating: GREEN; Mode of pathogenicity: None; Publications: 28211668; Phenotypes: X-linked complex neurodevelopmental disorder MONDO:0100148, neurodegeneration with brain iron accumulation 5 MONDO:0010476; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5399 WDR73 Kaitlyn Dianna Weldon reviewed gene: WDR73: Rating: GREEN; Mode of pathogenicity: None; Publications: 26123727; Phenotypes: Galloway-Mowat syndrome 1 MONDO:0033005; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 SMAD4 Claire Fryer-Smith reviewed gene: SMAD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843046, 22243968, 7296942, 8261650; Phenotypes: Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome MIM#175050, Myhre syndrome MIM#139210, Pancreatic cancer, somatic MIM#260350, Polyposis, juvenile intestinal MIM#174900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 WWOX Kaitlyn Dianna Weldon reviewed gene: WWOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 25411445, 24369382; Phenotypes: developmental and epileptic encephalopathy, 28 MONDO:0014533, autosomal recessive spinocerebellar ataxia 12 MONDO:0013687; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 XRCC4 Claire Fryer-Smith reviewed gene: XRCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25872942, 25839420, 18695064; Phenotypes: Short stature, microcephaly, and endocrine dysfunction MIM#616541; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 XRCC4 Kaitlyn Dianna Weldon reviewed gene: XRCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 25728776; Phenotypes: short stature, microcephaly, and endocrine dysfunction MONDO:0014686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 TUBB2B Claire Fryer-Smith reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 11425694, 23001566, 19465910, 22333901; Phenotypes: Cortical dysplasia, complex, with other brain malformations 7 MIM#610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 ZDHHC9 Kaitlyn Dianna Weldon reviewed gene: ZDHHC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 17436253; Phenotypes: Syndromic X-linked intellectual disability Raymond type MONDO:0010427; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5399 ZFYVE26 Kaitlyn Dianna Weldon reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301682; Phenotypes: hereditary spastic paraplegia 15 MONDO:0010044; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5399 ZIC2 Kaitlyn Dianna Weldon reviewed gene: ZIC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21940735; Phenotypes: holoprosencephaly 5 MONDO:0012322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TSC1 Claire Fryer-Smith reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10533067, 18830229, 15798777, 17304050; Phenotypes: Tuberous sclerosis-1 MIM#191100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 TSC2 Claire Fryer-Smith reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 14985384, 10533067, 10205261, 17304050; Phenotypes: Tuberous sclerosis-2 MIM#613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 NR2F2 Achchuthan Shanmugasundram reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37500725; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5399 GABBR1 Zornitza Stark Phenotypes for gene: GABBR1 were changed from Neurodevelopmental disorder, GABBR1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and variable cognitive abnormalities, MIM#620502
Intellectual disability syndromic and non-syndromic v0.5398 TAB2 Zornitza Stark Marked gene: TAB2 as ready
Intellectual disability syndromic and non-syndromic v0.5398 TAB2 Zornitza Stark Gene: tab2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5398 TAB2 Zornitza Stark Classified gene: TAB2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5398 TAB2 Zornitza Stark Gene: tab2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5397 FTCD Bryony Thompson Marked gene: FTCD as ready
Intellectual disability syndromic and non-syndromic v0.5397 FTCD Bryony Thompson Gene: ftcd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5397 FTCD Bryony Thompson Phenotypes for gene: FTCD were changed from to Glutamate formiminotransferase deficiency MIM#229100
Intellectual disability syndromic and non-syndromic v0.5396 FTCD Bryony Thompson Publications for gene: FTCD were set to
Intellectual disability syndromic and non-syndromic v0.5395 FTCD Bryony Thompson Mode of inheritance for gene: FTCD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5394 FTCD Bryony Thompson Classified gene: FTCD as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5394 FTCD Bryony Thompson Added comment: Comment on list classification: According to IEMbase this gene is associated with a benign form of disorder of folate metabolism with no clinical significance
Intellectual disability syndromic and non-syndromic v0.5394 FTCD Bryony Thompson Gene: ftcd has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5393 COL4A3BP Zornitza Stark Phenotypes for gene: COL4A3BP were changed from Mental retardation, autosomal dominant 34, MIM# 616351 to Intellectual developmental disorder 34 (MIM#616351)
Intellectual disability syndromic and non-syndromic v0.5392 COL4A3BP Zornitza Stark Publications for gene: COL4A3BP were set to 25533962
Intellectual disability syndromic and non-syndromic v0.5391 COL4A3BP Zornitza Stark Mode of pathogenicity for gene: COL4A3BP was changed from to Other
Intellectual disability syndromic and non-syndromic v0.5390 COL4A3BP Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT; to: - current HGNC symbol: CERT1
- Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT
Intellectual disability syndromic and non-syndromic v0.5390 COL4A3BP Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity,
which was corrected by pharmacological inhibition of CERT; to: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT
Intellectual disability syndromic and non-syndromic v0.5390 COL4A3BP Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity,
which was corrected by pharmacological inhibition of CERT; to: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo.
- Several variants transfected into HeLa cells demonstrated gain of CERT activity
- CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity,
which was corrected by pharmacological inhibition of CERT
Intellectual disability syndromic and non-syndromic v0.5390 COL4A3BP Ee Ming Wong reviewed gene: COL4A3BP: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 36976648; Phenotypes: Intellectual developmental disorder 34 (MIM#616351); Mode of inheritance: None; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Rylee Peters changed review comment from: 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 has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature; to: 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 to severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Ain Roesley Marked gene: RAB5C as ready
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Ain Roesley Classified gene: RAB5C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5390 RAB5C Ain Roesley Gene: rab5c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5389 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5389 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5388 AXIN1 Elena Savva Classified gene: AXIN1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5388 AXIN1 Elena Savva Gene: axin1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5387 RAB5C Rylee Peters gene: RAB5C was added
gene: RAB5C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RAB5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB5C were set to PMID: 37552066
Phenotypes for gene: RAB5C were set to Neurodevelopmental disorder MONDO:0700092, RAB5C-related
Penetrance for gene: RAB5C were set to Complete
Review for gene: RAB5C was set to GREEN
gene: RAB5C was marked as current diagnostic
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 has mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5387 AXIN1 Elena Savva Marked gene: AXIN1 as ready
Intellectual disability syndromic and non-syndromic v0.5387 AXIN1 Elena Savva Gene: axin1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5387 COL4A3BP Zornitza Stark Tag new gene name tag was added to gene: COL4A3BP.
Intellectual disability syndromic and non-syndromic v0.5387 AXIN1 Elena Savva gene: AXIN1 was added
gene: AXIN1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AXIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AXIN1 were set to PMID: 37582359
Phenotypes for gene: AXIN1 were set to Syndromic disease, (MONDO:0002254), AXIN1-related
Review for gene: AXIN1 was set to GREEN
Added comment: PMID: 37582359
- four families (7 individuals) with three homozygous truncating variants.
- all variant shown to result in reduced protein, though 1/3 would be NMD predicted
- Probands had macrocephaly (4/6), GDD (3/7), hip dysplasia (5/6), cardiac anomalies eg. VSD/ASD (3/7), cranial hyperostosis and vertebral endplate sclerosis
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5386 PPP1R3F Zornitza Stark Marked gene: PPP1R3F as ready
Intellectual disability syndromic and non-syndromic v0.5386 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5386 PPP1R3F Zornitza Stark Classified gene: PPP1R3F as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5386 PPP1R3F Zornitza Stark Gene: ppp1r3f has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5385 PPP1R3F Andrew Fennell gene: PPP1R3F was added
gene: PPP1R3F was added to Intellectual disability syndromic and non-syndromic. 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 syndromic and non-syndromic v0.5385 ATM Zornitza Stark Marked gene: ATM as ready
Intellectual disability syndromic and non-syndromic v0.5385 ATM Zornitza Stark Gene: atm has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5385 ATM Zornitza Stark Phenotypes for gene: ATM were changed from to Ataxia-telangiectasia, MIM#208900
Intellectual disability syndromic and non-syndromic v0.5384 ATM Zornitza Stark Classified gene: ATM as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5384 ATM Zornitza Stark Gene: atm has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5383 ATM Zornitza Stark edited their review of gene: ATM: Added comment: Progressive cerebellar dysfunction. Intellectual ability is typically normal. However, learning can be impaired due to motor and speech difficulties.; Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.5383 ATM Zornitza Stark reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ataxia-telangiectasia, MIM#208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5383 SOX11 Zornitza Stark Phenotypes for gene: SOX11 were changed from Coffin-Siris syndrome 9, OMIM # 615866 to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Intellectual disability syndromic and non-syndromic v0.5382 SOX11 Zornitza Stark Publications for gene: SOX11 were set to 24886874; 33785884; 33430815; 33086258; 31530938
Intellectual disability syndromic and non-syndromic v0.5381 SOX11 Zornitza Stark reviewed gene: SOX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29459093, 24886874, 33086258, 33785884, 35642566, 35341651; Phenotypes: Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5381 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5381 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5380 ATP5O Zornitza Stark Classified gene: ATP5O as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5380 ATP5O Zornitza Stark Gene: atp5o has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5379 ATP5O Zornitza Stark Marked gene: ATP5O as ready
Intellectual disability syndromic and non-syndromic v0.5379 ATP5O Zornitza Stark Gene: atp5o has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5379 ATP5O Zornitza Stark gene: ATP5O was added
gene: ATP5O was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 35621276; 34954817
Phenotypes for gene: ATP5O were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 7, MIM# 620359
Review for gene: ATP5O was set to GREEN
Added comment: Three unrelated families reported. Presenting features included DD, hypotonia, seizures.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5378 HIKESHI Zornitza Stark Marked gene: HIKESHI as ready
Intellectual disability syndromic and non-syndromic v0.5378 HIKESHI Zornitza Stark Gene: hikeshi has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5378 HIKESHI Zornitza Stark Classified gene: HIKESHI as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5378 HIKESHI Zornitza Stark Gene: hikeshi has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5377 HIKESHI Zornitza Stark gene: HIKESHI was added
gene: HIKESHI was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: HIKESHI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIKESHI were set to 34111619; 26545878
Phenotypes for gene: HIKESHI were set to Leukodystrophy, hypomyelinating, 13, MIM# 616881
Review for gene: HIKESHI was set to GREEN
Added comment: Over 10 individuals reported with recurrent homozygous c.160G>C;p.(Val54Leu) variant, high carrier frequency in the Ashkenazi Jewish population. Optic atrophy reported in several.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5376 FAM111A Zornitza Stark Marked gene: FAM111A as ready
Intellectual disability syndromic and non-syndromic v0.5376 FAM111A Zornitza Stark Gene: fam111a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5376 FAM111A Zornitza Stark Phenotypes for gene: FAM111A were changed from to Kenny-Caffey syndrome, type 2, MIM# 127000
Intellectual disability syndromic and non-syndromic v0.5375 FAM111A Zornitza Stark Mode of inheritance for gene: FAM111A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5374 FAM111A Zornitza Stark Classified gene: FAM111A as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5374 FAM111A Zornitza Stark Gene: fam111a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5373 FAM111A Zornitza Stark reviewed gene: FAM111A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Kenny-Caffey syndrome, type 2, MIM# 127000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5373 RAP1B Zornitza Stark Phenotypes for gene: RAP1B were changed from RAP1B‐associated phenotype, no OMIM # to Syndromic disease, MONDO:0002254, RAP1B-related
Intellectual disability syndromic and non-syndromic v0.5372 RAP1B Zornitza Stark edited their review of gene: RAP1B: Changed phenotypes: Syndromic disease, MONDO:0002254, RAP1B-related
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Tag new gene name tag was added to gene: ATP5E.
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Marked gene: ATP5E as ready
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Classified gene: ATP5E as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5372 ATP5E Zornitza Stark Gene: atp5e has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5371 PTCD3 Zornitza Stark Marked gene: PTCD3 as ready
Intellectual disability syndromic and non-syndromic v0.5371 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5371 PTCD3 Zornitza Stark Classified gene: PTCD3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5371 PTCD3 Zornitza Stark Gene: ptcd3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5370 PTCD3 Zornitza Stark gene: PTCD3 was added
gene: PTCD3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCD3 were set to 30607703; 19427859; 36450274
Phenotypes for gene: PTCD3 were set to Combined oxidative phosphorylation deficiency-51, MIM#619057; Intellectual disability; optic atrophy; Leigh-like syndrome
Review for gene: PTCD3 was set to GREEN
Added comment: Four families and functional data. ID is a feature.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.5369 ASS1 Zornitza Stark Marked gene: ASS1 as ready
Intellectual disability syndromic and non-syndromic v0.5369 ASS1 Zornitza Stark Gene: ass1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5369 ASS1 Zornitza Stark Phenotypes for gene: ASS1 were changed from to Citrullinemia MIM#215700
Intellectual disability syndromic and non-syndromic v0.5368 ASS1 Zornitza Stark Mode of inheritance for gene: ASS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5367 ASS1 Zornitza Stark reviewed gene: ASS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Citrullinemia MIM#215700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5367 ASPA Zornitza Stark Marked gene: ASPA as ready
Intellectual disability syndromic and non-syndromic v0.5367 ASPA Zornitza Stark Gene: aspa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5367 ASPA Zornitza Stark Phenotypes for gene: ASPA were changed from to Canavan disease MIM#271900
Intellectual disability syndromic and non-syndromic v0.5366 ASPA Zornitza Stark Mode of inheritance for gene: ASPA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5365 ASPA Zornitza Stark reviewed gene: ASPA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Canavan disease MIM#271900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5365 ARX Zornitza Stark Marked gene: ARX as ready
Intellectual disability syndromic and non-syndromic v0.5365 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5365 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to Lissencephaly, X-linked 2, MIM# 300215
Intellectual disability syndromic and non-syndromic v0.5364 ARX Zornitza Stark Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5363 ARX Zornitza Stark reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly, X-linked 2, MIM# 300215; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5363 ARV1 Zornitza Stark Marked gene: ARV1 as ready
Intellectual disability syndromic and non-syndromic v0.5363 ARV1 Zornitza Stark Gene: arv1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5363 ARV1 Zornitza Stark Phenotypes for gene: ARV1 were changed from to Developmental and epileptic encephalopathy 38, MIM# 617020
Intellectual disability syndromic and non-syndromic v0.5362 ARV1 Zornitza Stark Publications for gene: ARV1 were set to
Intellectual disability syndromic and non-syndromic v0.5361 ARV1 Zornitza Stark Mode of inheritance for gene: ARV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5360 ARV1 Zornitza Stark reviewed gene: ARV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35227294, 27270415, 25558065; Phenotypes: Developmental and epileptic encephalopathy 38, MIM# 617020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5360 ARID1A Zornitza Stark Marked gene: ARID1A as ready
Intellectual disability syndromic and non-syndromic v0.5360 ARID1A Zornitza Stark Gene: arid1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5360 ARID1A Zornitza Stark Phenotypes for gene: ARID1A were changed from to Coffin-Siris syndrome 2 (MIM#614607)
Intellectual disability syndromic and non-syndromic v0.5359 ARID1A Zornitza Stark Publications for gene: ARID1A were set to
Intellectual disability syndromic and non-syndromic v0.5358 ARID1A Zornitza Stark Mode of inheritance for gene: ARID1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5357 UBAP2L Zornitza Stark Phenotypes for gene: UBAP2L were changed from Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; 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, MIM# 620494; 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
Intellectual disability syndromic and non-syndromic v0.5356 UBAP2L Zornitza Stark edited their review of gene: UBAP2L: Changed phenotypes: Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, MIM# 620494
Intellectual disability syndromic and non-syndromic v0.5356 AP3B1 Zornitza Stark Marked gene: AP3B1 as ready
Intellectual disability syndromic and non-syndromic v0.5356 AP3B1 Zornitza Stark Gene: ap3b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5356 AP3B1 Zornitza Stark Phenotypes for gene: AP3B1 were changed from to Hermansky-Pudlak syndrome 2, MIM# 608233; MONDO:0011997
Intellectual disability syndromic and non-syndromic v0.5355 AP3B1 Zornitza Stark Publications for gene: AP3B1 were set to
Intellectual disability syndromic and non-syndromic v0.5354 AP3B1 Zornitza Stark Mode of inheritance for gene: AP3B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5353 AP3B1 Zornitza Stark reviewed gene: AP3B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10024875, 11809908, 14566336; Phenotypes: Hermansky-Pudlak syndrome 2, MIM# 608233, MONDO:0011997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5353 AMT Zornitza Stark Marked gene: AMT as ready
Intellectual disability syndromic and non-syndromic v0.5353 AMT Zornitza Stark Gene: amt has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5353 AMT Zornitza Stark Phenotypes for gene: AMT were changed from to Glycine encephalopathy MIM#605899
Intellectual disability syndromic and non-syndromic v0.5352 AMT Zornitza Stark Mode of inheritance for gene: AMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5351 AMT Zornitza Stark reviewed gene: AMT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycine encephalopathy MIM#605899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5351 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Intellectual disability syndromic and non-syndromic v0.5351 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5351 ALDH18A1 Zornitza Stark Phenotypes for gene: ALDH18A1 were changed from to Spastic paraplegia 9B, autosomal recessive, MIM# 616586
Intellectual disability syndromic and non-syndromic v0.5350 ALDH18A1 Zornitza Stark Mode of inheritance for gene: ALDH18A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5349 ALDH18A1 Zornitza Stark reviewed gene: ALDH18A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 9B, autosomal recessive, MIM# 616586; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5349 AIFM1 Zornitza Stark Marked gene: AIFM1 as ready
Intellectual disability syndromic and non-syndromic v0.5349 AIFM1 Zornitza Stark Gene: aifm1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5349 AIFM1 Zornitza Stark Phenotypes for gene: AIFM1 were changed from to Combined oxidative phosphorylation deficiency 6, 300816; Cowchock syndrome, 310490; Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232
Intellectual disability syndromic and non-syndromic v0.5348 AIFM1 Zornitza Stark Mode of inheritance for gene: AIFM1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5347 AIFM1 Zornitza Stark reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 6, 300816, Cowchock syndrome, 310490, Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5347 ADSL Zornitza Stark Marked gene: ADSL as ready
Intellectual disability syndromic and non-syndromic v0.5347 ADSL Zornitza Stark Gene: adsl has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5347 ADSL Zornitza Stark Phenotypes for gene: ADSL were changed from to Adenylosuccinase deficiency, MIM# 103050
Intellectual disability syndromic and non-syndromic v0.5346 ADSL Zornitza Stark Mode of inheritance for gene: ADSL was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5345 ADSL Zornitza Stark reviewed gene: ADSL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adenylosuccinase deficiency, MIM# 103050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5345 ADGRG1 Zornitza Stark Marked gene: ADGRG1 as ready
Intellectual disability syndromic and non-syndromic v0.5345 ADGRG1 Zornitza Stark Gene: adgrg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5345 ADGRG1 Zornitza Stark Phenotypes for gene: ADGRG1 were changed from to Polymicrogyria, bilateral frontoparietal, MIM# 606854
Intellectual disability syndromic and non-syndromic v0.5344 ADGRG1 Zornitza Stark Publications for gene: ADGRG1 were set to
Intellectual disability syndromic and non-syndromic v0.5343 ADGRG1 Zornitza Stark Mode of inheritance for gene: ADGRG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5342 ADGRG1 Zornitza Stark Tag 5'UTR tag was added to gene: ADGRG1.
Intellectual disability syndromic and non-syndromic v0.5342 ADGRG1 Zornitza Stark reviewed gene: ADGRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16240336; Phenotypes: Polymicrogyria, bilateral frontoparietal 606854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5342 NEUROG1 Zornitza Stark Marked gene: NEUROG1 as ready
Intellectual disability syndromic and non-syndromic v0.5342 NEUROG1 Zornitza Stark Gene: neurog1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5342 NEUROG1 Zornitza Stark Classified gene: NEUROG1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5342 NEUROG1 Zornitza Stark Gene: neurog1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5341 NEUROG1 Zornitza Stark gene: NEUROG1 was added
gene: NEUROG1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NEUROG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Phenotypes for gene: NEUROG1 were set to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Review for gene: NEUROG1 was set to GREEN
Added comment: There are four unrelated cases reported with global developmental delay/ intellectual disability.

PMID:23419067 - A homozygous micro deletion of NEUROG1 was identified in a six year-old boy presenting with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild global developmental delay. His IQ was normal.

PMID:26077850 - A homozygous NEUROG1 variant (p.Arg116Leu) was identified in a 12 year-old boy presented with syndromic corneal opacity, mild intellectual disability and absent corneal reflex.

PMID:33439489 - A homozygous loss-of-function variant (p.Glu68Ter) was identified in a 12 year-old boy presenting with hypotonia, global developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. This patient had a global IQ of 62 at the age of ten.

PMID:36647078 - A female proband was identified with a novel homozygous truncating frameshift variant (p.Thr78ProfsTer122 and was reported with profound global developmental delay, autism spectrum disorder, hearing loss, corneal opacity and no eye blinking. Her sister also had a similar, but less severe phenotype and also harboured the same variant at homozygous state.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5340 SRSF1 Zornitza Stark Phenotypes for gene: SRSF1 were changed from Neurodevelopmental disorder, SRSF1-related MONDO:0700092 to Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 620489
Intellectual disability syndromic and non-syndromic v0.5339 SRSF1 Zornitza Stark reviewed gene: SRSF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 620489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5339 CCDC115 Elena Savva Classified gene: CCDC115 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5339 CCDC115 Elena Savva Gene: ccdc115 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5339 CCDC115 Elena Savva Classified gene: CCDC115 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5339 CCDC115 Elena Savva Gene: ccdc115 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5338 CCDC115 Elena Savva Marked gene: CCDC115 as ready
Intellectual disability syndromic and non-syndromic v0.5338 CCDC115 Elena Savva Gene: ccdc115 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5338 CCDC115 Elena Savva gene: CCDC115 was added
gene: CCDC115 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CCDC115 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CCDC115 were set to Congenital disorder of glycosylation, type IIo MIM# 616828
Review for gene: CCDC115 was set to GREEN
Added comment: Added following CAM discussion
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5337 FBXO31 Ain Roesley reviewed gene: FBXO31: Rating: AMBER; Mode of pathogenicity: None; Publications: 35019165, 24623383; Phenotypes: intellectual developmental disorder 45 (MIM#615979); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5337 ACTB Zornitza Stark Phenotypes for gene: ACTB were changed from Baraitser-Winter syndrome 1, MIM# 243310; ACTB-related neurodevelopment disorder to Baraitser-Winter syndrome 1, MIM# 243310; Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475; ACTB-related neurodevelopment disorder
Intellectual disability syndromic and non-syndromic v0.5336 ACTB Zornitza Stark edited their review of gene: ACTB: Changed phenotypes: Baraitser-Winter syndrome 1 243310, ACTB-related neurodevelopment disorder, Thrombocytopenia 8, with dysmorphic features and developmental delay, MIM# 620475
Intellectual disability syndromic and non-syndromic v0.5336 ATP6V0C Zornitza Stark Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, with or without developmental delay, MIM#620465; Epilepsy; Intellectual Disability; microcephaly
Intellectual disability syndromic and non-syndromic v0.5335 ZFHX4 Ain Roesley Phenotypes for gene: ZFHX4 were changed from Developmental disorders; intellectual disability, dysmorphic features to neurodevelopmental disorder, ZFHX4-related (MONDO:0700092)
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Marked gene: HNRNPC as ready
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Classified gene: HNRNPC as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5334 HNRNPC Zornitza Stark Gene: hnrnpc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5333 HNRNPC Zornitza Stark gene: HNRNPC was added
gene: HNRNPC was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HNRNPC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPC were set to 37541189
Phenotypes for gene: HNRNPC were set to Neurodevelopmental disorder (MONDO:0700092), HNRNPC-related
Review for gene: HNRNPC was set to GREEN
Added comment: 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five had an identical in-frame deletion of nine amino acids in the extreme C terminus.

Supportive functional data; haploinsufficiency is the mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5332 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5331 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5330 PSMC3 Zornitza Stark Phenotypes for gene: PSMC3 were changed from Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354 to neurodevelopmental disorder, MONDO:0700092, PSMC3-related; Deafness, cataract, impaired intellectual development, and polyneuropathy, MIM#619354
Intellectual disability syndromic and non-syndromic v0.5329 PSMC3 Zornitza Stark Publications for gene: PSMC3 were set to 32500975
Intellectual disability syndromic and non-syndromic v0.5328 PSMC3 Zornitza Stark Mode of inheritance for gene: PSMC3 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5327 PSMC3 Zornitza Stark Classified gene: PSMC3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5327 PSMC3 Zornitza Stark Gene: psmc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5326 EMC1 Zornitza Stark Publications for gene: EMC1 were set to 26942288; 29271071
Intellectual disability syndromic and non-syndromic v0.5325 EMC1 Zornitza Stark Mode of inheritance for gene: EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5324 PSMC3 Achchuthan Shanmugasundram reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37256937; Phenotypes: neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5324 EMC1 Chern Lim reviewed gene: EMC1: Rating: ; Mode of pathogenicity: None; Publications: 35234901, 26942288; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5324 SLC4A10 Krithika Murali Classified gene: SLC4A10 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5324 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5323 SLC4A10 Krithika Murali Marked gene: SLC4A10 as ready
Intellectual disability syndromic and non-syndromic v0.5323 SLC4A10 Krithika Murali Gene: slc4a10 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Marked gene: AQP4 as ready
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5323 AQP4 Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Intellectual disability syndromic and non-syndromic v0.5322 AQP4 Zornitza Stark Classified gene: AQP4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5322 AQP4 Zornitza Stark Gene: aqp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Marked gene: EZH1 as ready
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5321 EZH1 Zornitza Stark Phenotypes for gene: EZH1 were changed from to Neurodevelopmental disorder (MONDO:0700092), EZH1-related
Intellectual disability syndromic and non-syndromic v0.5320 EZH1 Zornitza Stark Publications for gene: EZH1 were set to
Intellectual disability syndromic and non-syndromic v0.5319 EZH1 Zornitza Stark Classified gene: EZH1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5319 EZH1 Zornitza Stark Gene: ezh1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Marked gene: PHF5A as ready
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Classified gene: PHF5A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5318 PHF5A Zornitza Stark Gene: phf5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 AQP4 Lucy Spencer gene: AQP4 was added
gene: AQP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AQP4 were set to 37143309
Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448
Review for gene: AQP4 was set to AMBER
Added comment: PMID: 37143309
Cohort patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit.

Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5317 PHF5A Daniel Flanagan gene: PHF5A was added
gene: PHF5A was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF5A were set to PMID: 37422718
Phenotypes for gene: PHF5A were set to Neurodevelopmental disorder (MONDO#0700092), PHF5A-related
Review for gene: PHF5A was set to GREEN
Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects, and heart defects (3/9), inguinal hernia (3/9), and sacral dimple (3/9). Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Marked gene: GPRC5B as ready
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Classified gene: GPRC5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5317 GPRC5B Ain Roesley Gene: gprc5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5316 EZH1 Dean Phelan reviewed gene: EZH1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 37433783; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), EZH1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5316 NAA30 Zornitza Stark Marked gene: NAA30 as ready
Intellectual disability syndromic and non-syndromic v0.5316 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5316 NAA30 Zornitza Stark Phenotypes for gene: NAA30 were changed from to neurodevelopmental disorder, MONDO:0700092, NAA30-related
Intellectual disability syndromic and non-syndromic v0.5315 NAA30 Zornitza Stark Mode of inheritance for gene: NAA30 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5314 NAA30 Zornitza Stark Classified gene: NAA30 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5314 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5314 NAA30 Zornitza Stark Classified gene: NAA30 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5314 NAA30 Zornitza Stark Gene: naa30 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5313 GPRC5B Lucy Spencer gene: GPRC5B was added
gene: GPRC5B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPRC5B were set to PMID: 37143309
Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 MIM#620447
Review for gene: GPRC5B was set to GREEN
Added comment: PMID: 37143309
Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, spasticity, ataxia and dystonia, seizures, all had varying degrees of cognitive deficits. MRI showed MLC, abnormal and swollen cerebral white matter.

Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5313 NAA30 Sarah Pantaleo edited their review of gene: NAA30: Changed phenotypes: neurodevelopmental disorder, MONDO:0700092, NAA30-related
Intellectual disability syndromic and non-syndromic v0.5313 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5312 SLC4A10 Krithika Murali gene: SLC4A10 was added
gene: SLC4A10 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to PMID: 37459438
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorderMONDO:0700092, SLC4A10-related
Review for gene: SLC4A10 was set to GREEN
Added comment: PMID: 37459438 Fasham et al 2023 (Brain) report 10 affected individuals from 5 unrelated families with biallelic LoF variants in this gene with a novel neurodevelopmental disorder.

Phenotypic features include hypotonia in infancy, delayed psychomotor development, typically severe ID, progressive postnatal microcephaly, ASD traits, corpus callosal abnormalities and 'slit-like' lateral ventricles. These phenotypic features were recapitulated in knockout mice with additional supportive functional studies.

Isolated seizures was reported in 2/10 cases.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5312 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to 37451268
Intellectual disability syndromic and non-syndromic v0.5311 NAA30 Sarah Pantaleo gene: NAA30 was added
gene: NAA30 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NAA30 was set to Unknown
Publications for gene: NAA30 were set to PMID: 37387332
Penetrance for gene: NAA30 were set to unknown
Review for gene: NAA30 was set to RED
Added comment: Report a de novo heterozygous NAA30 nonsense variant c.244C>T, p.(Gln82*) in a 5yo boy with GDD, ASD, hypotonia, seizures, tracheal cleft and recurrent respiratory infections. Seizures resolved after two weeks of life. Family history of ASD in older sister. Epilepsy in mother, childhood onset.

Biochemical studies performed to assess the functional impact of the premature stop codon on catalytic activity. The variant was found to completely disrupt N-terminal acetyltransferase activity using an in vitro acetylation assay.

Variant de novo, “in a gene sensitive to loss of heterozygosity”. Limitation of study - have not established whether this gene variant acts in a dominant or recessive manner.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5311 PIP5K1C Elena Savva Publications for gene: PIP5K1C were set to
Intellectual disability syndromic and non-syndromic v0.5310 KDM4B Sarah Pantaleo reviewed gene: KDM4B: Rating: ; Mode of pathogenicity: None; Publications: PMID: 37526414; Phenotypes: Intellectual developmental disorder, autosomal dominant 65, MIM#619320; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5310 EZH1 Dean Phelan gene: EZH1 was added
gene: EZH1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EZH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5310 EIF4A2 Zornitza Stark Phenotypes for gene: EIF4A2 were changed from Neurodevelopmental disorder (MONDO:0700092), EIF4A2-related to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, MIM# 620455
Intellectual disability syndromic and non-syndromic v0.5309 TMEM63B Zornitza Stark Marked gene: TMEM63B as ready
Intellectual disability syndromic and non-syndromic v0.5309 TMEM63B Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5309 TMEM63B Zornitza Stark Classified gene: TMEM63B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5309 TMEM63B Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5308 TMEM63B Zornitza Stark gene: TMEM63B was added
gene: TMEM63B was added to Intellectual disability syndromic and non-syndromic. 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, TMEM63B-related
Review for gene: TMEM63B was set to GREEN
Added comment: 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. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Marked gene: DHX9 as ready
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Added comment: Comment when marking as ready: LoF variants caused mild NDD phenotypes and nuclear localization signal (NLS) missense variants caused severe NDD. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress.
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Marked gene: DHX9 as ready
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Classified gene: DHX9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5307 DHX9 Zornitza Stark Gene: dhx9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5306 DHX9 Zornitza Stark gene: DHX9 was added
gene: DHX9 was added to Intellectual disability syndromic and non-syndromic. 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, DHX9-related
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). The three cases with CMT presented with adult-onset axonal neuropathy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5305 NLGN4X Zornitza Stark Publications for gene: NLGN4X were set to 12669065; 18231125; 10071191; 29428674
Intellectual disability syndromic and non-syndromic v0.5304 NLGN4X Zornitza Stark Classified gene: NLGN4X as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5304 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5303 WBP4 Zornitza Stark Marked gene: WBP4 as ready
Intellectual disability syndromic and non-syndromic v0.5303 WBP4 Zornitza Stark Gene: wbp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5303 WBP4 Zornitza Stark Phenotypes for gene: WBP4 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, WBP4-related
Intellectual disability syndromic and non-syndromic v0.5302 KDM2A Zornitza Stark Marked gene: KDM2A as ready
Intellectual disability syndromic and non-syndromic v0.5302 KDM2A Zornitza Stark Gene: kdm2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5302 KDM2A Zornitza Stark Phenotypes for gene: KDM2A were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, KDM2A-related
Intellectual disability syndromic and non-syndromic v0.5301 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Intellectual disability syndromic and non-syndromic v0.5301 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5301 PIP5K1C Zornitza Stark Phenotypes for gene: PIP5K1C were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, PIP5K1C-related
Intellectual disability syndromic and non-syndromic v0.5300 INTS13 Zornitza Stark Marked gene: INTS13 as ready
Intellectual disability syndromic and non-syndromic v0.5300 INTS13 Zornitza Stark Gene: ints13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5300 INTS13 Zornitza Stark Phenotypes for gene: INTS13 were changed from Oral-facial-digital syndrome to Oral-facial-digital syndrome, MONDO:0015375, INTS13-related
Intellectual disability syndromic and non-syndromic v0.5299 TEFM Zornitza Stark Marked gene: TEFM as ready
Intellectual disability syndromic and non-syndromic v0.5299 TEFM Zornitza Stark Gene: tefm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5299 TEFM Zornitza Stark Classified gene: TEFM as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5299 TEFM Zornitza Stark Gene: tefm has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5298 TEFM Zornitza Stark gene: TEFM was added
gene: TEFM was added to Intellectual disability syndromic and non-syndromic. 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, MIM# 620451
Review for gene: TEFM was set to GREEN
Added comment: Seven individuals from 5 families reported. Presentation predominantly with encephalopathy, seizures and ID, in addition to lactic acidosis.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5297 CYHR1 Zornitza Stark Marked gene: CYHR1 as ready
Intellectual disability syndromic and non-syndromic v0.5297 CYHR1 Zornitza Stark Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5297 CYHR1 Zornitza Stark Phenotypes for gene: CYHR1 were changed from Neurodevelopmental disorder and microcephaly to Neurodevelopmental disorder and microcephaly, MONDO:0700092, CYHR1-related
Intellectual disability syndromic and non-syndromic v0.5296 TSPOAP1 Zornitza Stark Phenotypes for gene: TSPOAP1 were changed from Dystonia, intellectual disability and cerebellar atrophy to Dystonia 22, MIM# 620453
Intellectual disability syndromic and non-syndromic v0.5295 TSPOAP1 Zornitza Stark reviewed gene: TSPOAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 22, MIM# 620453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5295 TAF4 Zornitza Stark Phenotypes for gene: TAF4 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF4-related to Intellectual developmental disorder, autosomal dominant 73, MIM# 620450
Intellectual disability syndromic and non-syndromic v0.5294 TAF4 Zornitza Stark edited their review of gene: TAF4: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 73, MIM# 620450
Intellectual disability syndromic and non-syndromic v0.5294 GPATCH11 Zornitza Stark Marked gene: GPATCH11 as ready
Intellectual disability syndromic and non-syndromic v0.5294 GPATCH11 Zornitza Stark Gene: gpatch11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5294 GPATCH11 Zornitza Stark Phenotypes for gene: GPATCH11 were changed from Leber congenital amaurosis and developmental delay to Neurodevelopmental disorder, MONDO:0700092, GPATCH11-related; Leber congenital amaurosis and developmental delay
Intellectual disability syndromic and non-syndromic v0.5293 GPATCH11 Zornitza Stark Classified gene: GPATCH11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5293 GPATCH11 Zornitza Stark Gene: gpatch11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5292 KCNA3 Zornitza Stark Marked gene: KCNA3 as ready
Intellectual disability syndromic and non-syndromic v0.5292 KCNA3 Zornitza Stark Gene: kcna3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5292 KCNA3 Zornitza Stark Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, KCNA3-related
Intellectual disability syndromic and non-syndromic v0.5291 FSD1L Zornitza Stark Marked gene: FSD1L as ready
Intellectual disability syndromic and non-syndromic v0.5291 FSD1L Zornitza Stark Gene: fsd1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5291 FSD1L Zornitza Stark Phenotypes for gene: FSD1L were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, FSD1L-related
Intellectual disability syndromic and non-syndromic v0.5290 DENND5B Zornitza Stark Marked gene: DENND5B as ready
Intellectual disability syndromic and non-syndromic v0.5290 DENND5B Zornitza Stark Gene: dennd5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5290 DENND5B Zornitza Stark Phenotypes for gene: DENND5B were changed from Neurodevelopmental disorder with white matter anomalies to Neurodevelopmental disorder with white matter anomalies, MONDO:0700092, DENND5B-related
Intellectual disability syndromic and non-syndromic v0.5289 DMAP1 Zornitza Stark Marked gene: DMAP1 as ready
Intellectual disability syndromic and non-syndromic v0.5289 DMAP1 Zornitza Stark Gene: dmap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5289 DMAP1 Zornitza Stark Phenotypes for gene: DMAP1 were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, DMAP1-related
Intellectual disability syndromic and non-syndromic v0.5288 HCN2 Zornitza Stark Marked gene: HCN2 as ready
Intellectual disability syndromic and non-syndromic v0.5288 HCN2 Zornitza Stark Gene: hcn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5288 HCN2 Zornitza Stark Phenotypes for gene: HCN2 were changed from Febrile seizures, familial, 2 MIM#602477; Generalized epilepsy with febrile seizures plus, type 11 MIM#602477; {Epilepsy, idiopathic generalized, susceptibility to, 17} MIM#602477; Neurodevelopmental disorder (MONDO#0700092), HCN2-related to Neurodevelopmental disorder (MONDO#0700092), HCN2-related
Intellectual disability syndromic and non-syndromic v0.5287 HCN2 Zornitza Stark Classified gene: HCN2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5287 HCN2 Zornitza Stark Gene: hcn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5286 TTI1 Zornitza Stark Phenotypes for gene: TTI1 were changed from Neurodevelopmental disorder, MONDO:0700092, TTI1-related to Neurodevelopmental disorder with microcephaly and movement abnormalities, MIM# 620445
Intellectual disability syndromic and non-syndromic v0.5285 TTI1 Zornitza Stark Publications for gene: TTI1 were set to 26539891; 30315573
Intellectual disability syndromic and non-syndromic v0.5284 DCAF15 Zornitza Stark Marked gene: DCAF15 as ready
Intellectual disability syndromic and non-syndromic v0.5284 DCAF15 Zornitza Stark Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5284 DCAF15 Zornitza Stark Phenotypes for gene: DCAF15 were changed from Cornelia de Lange syndrome to Cornelia de Lange syndrome, MONDO:0016033, DCAF15-related
Intellectual disability syndromic and non-syndromic v0.5283 WBP4 Chirag Patel Classified gene: WBP4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5283 WBP4 Chirag Patel Gene: wbp4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5282 WBP4 Chirag Patel gene: WBP4 was added
gene: WBP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WBP4 were set to Neurodevelopmental disorder
Review for gene: WBP4 was set to GREEN
gene: WBP4 was marked as current diagnostic
Added comment: ESHG 2023:
11 individuals from 8 families with homozygous LOF variants in WBP4 gene (4 different variants). Presentation of severe DD and ID, hypotonia, abnormal outer ears, and varying congenital anomalies. WBP4 is spliceosome protein which binds/interacts with SNRNP200. In vivo and in vitro studies previously showed WBP4 enhances splicing and regulates alternative splicing. Patient fibroblasts showed loss of expression of WBP4. RNA sequencing analysis showed abnormal splicing patterns. Proposed spliceosomopathy.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5281 KDM2A Chirag Patel Classified gene: KDM2A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5281 KDM2A Chirag Patel Gene: kdm2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5280 KDM2A Chirag Patel gene: KDM2A was added
gene: KDM2A was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: KDM2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KDM2A were set to Neurodevelopmental disorder
Review for gene: KDM2A was set to GREEN
gene: KDM2A was marked as current diagnostic
Added comment: ESHG 2023:
14 patients with de novo HTZ variants in KDM2A (5 x truncating, 9 x missense)
Presentation with DD, ID (mild), seizures, growth retardation, and dysmorphism.

Functional studies:
-patient blood showed aberrant genome wide methylation profile - potential episignature
-HEK293T cells showed altered subcellular localisation of KDM2A
-Drosophila models showed variants caused neurotoxicity
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5279 PIP5K1C Chirag Patel Classified gene: PIP5K1C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5279 PIP5K1C Chirag Patel Gene: pip5k1c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5278 PIP5K1C Chirag Patel gene: PIP5K1C was added
gene: PIP5K1C was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIP5K1C were set to Neurodevelopmental disorder and microcephaly
Review for gene: PIP5K1C was set to GREEN
gene: PIP5K1C was marked as current diagnostic
Added comment: ESHG 2023:
9 unrelated patients with de novo missense variants in PIP5K1C (3 x recurrent variants).
Presentation with DD/ID (mod-profound), microcephaly, seizures, visual impairment, and dysmorphism.

PIP5K1C is one of the phosphoinositolides, which control membrane composition of organelles and varying cellular processes. Patient fibroblasts showed increased PI(4,5)P2 levels, altered PI(4,5)P2 composition of early endosomes, and impaired endocytosis trafficking. Drosophila models showed microcephaly and ocular phenotype.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5277 NSUN6 Chirag Patel changed review comment from: Sufficient evidence for upgrade; to: Drosophila KO showed locomotion defects and reduced learning ability. Sufficient evidence for upgrade
Intellectual disability syndromic and non-syndromic v0.5277 NSUN6 Chirag Patel Classified gene: NSUN6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5277 NSUN6 Chirag Patel Gene: nsun6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5276 NSUN6 Chirag Patel reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5276 INTS13 Chirag Patel Classified gene: INTS13 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5276 INTS13 Chirag Patel Gene: ints13 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5275 INTS13 Chirag Patel gene: INTS13 was added
gene: INTS13 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to PMID: 36229431
Phenotypes for gene: INTS13 were set to Oral-facial-digital syndrome
Review for gene: INTS13 was set to GREEN
Added comment: 2 families with 4 affected individuals with Oral-facial-digital (OFD) phenotype. Homozygosity mapping and WES found 2 homozygous variants in INTS13 gene. This is a subunit of the Integrator complex, which associates with RNA Polymerase II and cleaves nascent RNA to modulate gene expression. Variants segregated with disease. Depletion of INTS13 disrupts ciliogenesis in human cultured cells and causes dysregulation of a broad collection of ciliary genes. Knockdown in Xenopus embryos leads to motile cilia anomalies.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5274 DCAF15 Chirag Patel Classified gene: DCAF15 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5274 DCAF15 Chirag Patel Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5274 DCAF15 Chirag Patel Classified gene: DCAF15 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5274 DCAF15 Chirag Patel Gene: dcaf15 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5273 DCAF15 Chirag Patel gene: DCAF15 was added
gene: DCAF15 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DCAF15 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DCAF15 were set to Cornelia de Lange syndrome
Review for gene: DCAF15 was set to AMBER
Added comment: ESHG 2023:
3 unrelated cases with CdLS (1 x TOP with MCA, 1 x death @20mths, 1 x living child)
Features suggestive of CdLS - DD, microcephaly, CHD, dysmorphism, visual/hearing impairment.

WES identified recurrent de novo variant (p.Ser470Phe) in DCAF15 gene. This mediates ubiquitination and degradation of target proteins, and interacts with cohesin complex members (SMC1/SMC3).

Protein analysis from individuals showed increased accumulation of ubiquitination-modified proteins and SM3 (GOF mechanism). EpiSign analysis showed same DNA methylation pattern as other CdLS cases/genes. Zebrafish model showed reduced body length, reduced head size, reduced oligodendrocytes, heart defect, aberrant motor neurons, and abnormal response to visual/auditory stimuli.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5272 CYHR1 Chirag Patel Classified gene: CYHR1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5272 CYHR1 Chirag Patel Gene: cyhr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5271 CYHR1 Chirag Patel gene: CYHR1 was added
gene: CYHR1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: CYHR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYHR1 were set to Neurodevelopmental disorder and microcephaly
Review for gene: CYHR1 was set to AMBER
gene: CYHR1 was marked as current diagnostic
Added comment: ESHG 2023:
5 individuals from 3 families with biallelic LOF variants in CYHR1 (aka ZTRAF1). Presentation with microcephaly, hypotonia, DD, and ID. Expression studies showed mislocalisation of CYHR1. Mutant fibroblasts showed increased lysosomal markers and upregulated lysosomal proteins, leading to impaired autophagy. Zebrafish KO however did not show a phenotype.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5270 GPATCH11 Chirag Patel gene: GPATCH11 was added
gene: GPATCH11 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: GPATCH11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPATCH11 were set to Leber congenital amaurosis and developmental delay
Review for gene: GPATCH11 was set to GREEN
gene: GPATCH11 was marked as current diagnostic
Added comment: ESHG 2023:
3 families with 8 individuals with leber congenital amaurosis, developmental delay, language disorder, and behavioural issues.
GPATCH11 localises to nucleus and basal body of primary cilium (similar to other LCA genes).
Biallelic variants found in GPATCH11 - 1 splice variant common to all 3 families (1 other variant in 3rd family). Splice variant leads to loss of exon 4 (mRNA studies).
Mouse models showed i) abnormal rod/cone responses on ERG; ii) decreased outer nuclear layer in retina, and iii) abnormal associate/episodic memory
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5269 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5269 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5268 KCNA3 Chirag Patel Classified gene: KCNA3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5268 KCNA3 Chirag Patel Gene: kcna3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5267 KCNA3 Chirag Patel gene: KCNA3 was added
gene: KCNA3 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCNA3 were set to Neurodevelopmental disorder
Review for gene: KCNA3 was set to GREEN
gene: KCNA3 was marked as current diagnostic
Added comment: ESHG 2023:
10 individuals with de novo missense variants in KCNA3 (K+ channel)
Variable electrophysiology studies of effect of variants (5 x LOF, 4 x GOF, 1 no change)
Presentation: abnormal speech development (8/8), ID (6/8), epilepsy (5/8), and ASD (7/8)
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5266 FSD1L Chirag Patel Classified gene: FSD1L as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5266 FSD1L Chirag Patel Gene: fsd1l has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5265 FSD1L Chirag Patel gene: FSD1L was added
gene: FSD1L was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: FSD1L was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FSD1L were set to Neurodevelopmental disorder
Review for gene: FSD1L was set to GREEN
gene: FSD1L was marked as current diagnostic
Added comment: ESHG 2023:
8 families with biallelic missense/nonsense variants
Presentation only described 1 family/2 affecteds with DD, ID, spastic paraparesis, epilepsy, corpus callosum hypoplasia, and optic nerve hypoplasia

Functional assays:
-reduced expression of FSD1L in mature neurons (RNA studies)
-very low % mature neurons (neuronal differentiation)
-reduced neuronal migration
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5264 DENND5B Chirag Patel Classified gene: DENND5B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5264 DENND5B Chirag Patel Gene: dennd5b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5263 DENND5B Chirag Patel gene: DENND5B was added
gene: DENND5B was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DENND5B were set to Neurodevelopmental disorder with white matter anomalies
Review for gene: DENND5B was set to GREEN
gene: DENND5B was marked as current diagnostic
Added comment: ESHG 2023:
7 patients/7 families with de novo DENND5B variants (6 missense, 1 splice)
DD/ID (mod/profound)(7/7), white matter anomalies (6/7) hypotonia, epilepsy (3/7)

DENND5B acts as:
-GEF for activation of RAB proteins which are involved in membrane trafficking and neurotransmitter release
-regulator of lipid absorption and homeostasis

Functional studies showed loss of expression of DENND5B in fibroblasts, abnormal vesicle trafficking, and impaired lipid uptake and intracellular distribution
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5262 DMAP1 Chirag Patel Classified gene: DMAP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5262 DMAP1 Chirag Patel Gene: dmap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5261 DMAP1 Chirag Patel Classified gene: DMAP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5261 DMAP1 Chirag Patel Gene: dmap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5260 DMAP1 Chirag Patel gene: DMAP1 was added
gene: DMAP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: DMAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DMAP1 were set to Neurodevelopmental disorder
Review for gene: DMAP1 was set to GREEN
gene: DMAP1 was marked as current diagnostic
Added comment: ESHG 2023:
9 patients/8 families with bilallelic variants in DMAP1 (3 missense, 7 LOF)
All with DD, speech delay, hypotonia, and ID
Some with epilepsy (4/6), FTT (4/5), and brain malformations (3/5)
Drosophila showed abnormal behaviour pattern and bang sensitivity
Specific methylation episignature also seen
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5259 ITFG2 Chirag Patel Classified gene: ITFG2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5259 ITFG2 Chirag Patel Gene: itfg2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5258 ITFG2 Chirag Patel reviewed gene: ITFG2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5258 HCN2 Elena Savva gene: HCN2 was added
gene: HCN2 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: HCN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: HCN2 were set to Febrile seizures, familial, 2 MIM#602477; Generalized epilepsy with febrile seizures plus, type 11 MIM#602477; {Epilepsy, idiopathic generalized, susceptibility to, 17} MIM#602477; Neurodevelopmental disorder (MONDO#0700092), HCN2-related
Review for gene: HCN2 was set to AMBER
Added comment: ICG 2023 conference
- cohort of 20 individuals where >80% had a form of intellectual disability (half were severe) and/or seizures. Some had isolated intellectual disability, especially those with a recurring de novo p.E478del.
- Patients were both mono- and biallelic.
- Monoallelic individuals had de novo missense and an inframe deletion. Biallelic individuals had a mix of missense and PTC
Sources: Other
Intellectual disability syndromic and non-syndromic v0.5257 ZMYM3 Zornitza Stark Phenotypes for gene: ZMYM3 were changed from Neurodevelopmental disorder, MONDO:0700092, ZMYM3-related to Intellectual developmental disorder, X-linked 112, MIM# 301111
Intellectual disability syndromic and non-syndromic v0.5256 ZMYM3 Zornitza Stark reviewed gene: ZMYM3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 112, MIM# 301111; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.5256 SART3 Krithika Murali Classified gene: SART3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5256 SART3 Krithika Murali Gene: sart3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5255 SART3 Krithika Murali Marked gene: SART3 as ready
Intellectual disability syndromic and non-syndromic v0.5255 SART3 Krithika Murali Gene: sart3 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Classified gene: RPH3A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5255 RPH3A Elena Savva Gene: rph3a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5254 RPH3A Elena Savva Marked gene: RPH3A as ready
Intellectual disability syndromic and non-syndromic v0.5254 RPH3A Elena Savva Gene: rph3a has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5254 SART3 Daniel Flanagan edited their review of gene: SART3: Changed phenotypes: Neurodevelopmental disorder (MONDO#0700092), SART3-related, 46,XY disorder of sex development (MONDO:0020040), SART3-related
Intellectual disability syndromic and non-syndromic v0.5254 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5254 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Marked gene: DRG1 as ready
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Classified gene: DRG1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5253 DRG1 Krithika Murali Gene: drg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5252 SART3 Daniel Flanagan gene: SART3 was added
gene: SART3 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SART3 were set to PMID: 37296101
Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related, with 46,XY gonadal dysgenesis
Review for gene: SART3 was set to GREEN
Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG.

Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Classified gene: ERI1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5252 ERI1 Elena Savva Gene: eri1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva Marked gene: ERI1 as ready
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva Gene: eri1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5251 ERI1 Elena Savva gene: ERI1 was added
gene: ERI1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to Intellectual disability (MONDO#0001071), ERI1-related
Review for gene: ERI1 was set to GREEN
Added comment: PMID: 37352860 - 8 individuals from 7 unrelated families
- Patients with biallelic missense show a MORE severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly
- Patients with biallelic null/whole gene deletion had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly
- Patient chet for a missense and PTC variant has a blended phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, mild ID and failure to thrive

- Missense variants were functionally shown to not be able to rescue 5.8S rRNA processing in KO HeLa cells
- K/O mice had neonatal lethality with growth defects, brachydactyly. Skeletal-specific K/O had mild platyspondyly, had more in keeping with patients with null variants than missense

More severe phenotype hypothesised due to "exonuclease-dead proteins may compete for the target RNA molecules with other exonucleases that have functional redundancy
with ERI1, staying bound to those RNA molecules"
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5250 RPH3A Lucy Spencer gene: RPH3A was added
gene: RPH3A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RPH3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPH3A were set to 37403762; 29441694
Phenotypes for gene: RPH3A were set to Neurodevelopmental disorder (MONDO#0700092), RPH3A-related
Review for gene: RPH3A was set to GREEN
Added comment: PMID: 37403762- 6 patients with RPH3A variant. All 6 have ID, 4 have epilepsy, 2 with obesity, 1 with dysmorphic features. All 6 have missense variants, 3 shown to be de novo, the other 3 parents were not available for testing. I patient also had language and motor impairment, breathing issues and mixed hypo/hypertonia- he also had variants in CUL4B, PRKAG2, SCN4A, none of these genes cause seizures (which he had).

Patch clamp studies on 2 of the missense showed they increased either the number of NMDA receptors on neuron membrane surface or increased their conductance. Study suggests that the variants interrupt the normal role of RPH3A activity at the synaptic NMDAR complex which is needed for the induction of synaptic plasticity and NMDAR-dependant behaviours

Also previously 1 biallelic patient was reported, PMID: 29441694- 1 girl with learning disabilities, tremors, ataxia, hyperglycemia and muscle fatigability. Chet for 2 RPH3A missense. Functional analysis showed strong and marginal impairment of protein binding for each variant.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5250 DRG1 Dean Phelan gene: DRG1 was added
gene: DRG1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to PMID: 37179472
Phenotypes for gene: DRG1 were set to Neurodevelopmental disorder (MONDO:0700092), DRG1-related
Review for gene: DRG1 was set to GREEN
Added comment: PMID: 37179472
- Biallelic variants were identified in four affected individuals from three distinct families with neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature and craniofacial anomalies. Functional studies show the variants result in a loss of function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5250 INTS11 Zornitza Stark Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM# 620428
Intellectual disability syndromic and non-syndromic v0.5249 SRRM2 Zornitza Stark Publications for gene: SRRM2 were set to 33057194
Intellectual disability syndromic and non-syndromic v0.5248 SRRM2 Zornitza Stark Phenotypes for gene: SRRM2 were changed from neurodevelopmental disorder MONDO:0700092 SRRM2-related to Intellectual developmental disorder, autosomal dominant 72, MIM# 620439
Intellectual disability syndromic and non-syndromic v0.5247 GCSH Zornitza Stark Phenotypes for gene: GCSH were changed from Glycine encephalopathy MIM#605899; neurodevelopmental disorder MONDO#0700092, GCHS-related to Multiple mitochondrial dysfunctions syndrome 7, MIM# 620423
Intellectual disability syndromic and non-syndromic v0.5246 RHOBTB2 Zornitza Stark Publications for gene: RHOBTB2 were set to 29768694; 29276004
Intellectual disability syndromic and non-syndromic v0.5245 RHOBTB2 Zornitza Stark Mode of inheritance for gene: RHOBTB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5244 RHOBTB2 Zornitza Stark edited their review of gene: RHOBTB2: Added comment: PMID 37165955: 16 individuals with de novo heterozygous missense variants in the BTB domain region and a severe DEE as previously reported. In addition, 6 individuals with de novo missense variants in the GTPase domain and a more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences.
In addition, 9 families with observed bi-allelic splice-site and truncating variants with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well.; Changed publications: 29768694, 29276004, 37165955; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5244 MCM6 Zornitza Stark Marked gene: MCM6 as ready
Intellectual disability syndromic and non-syndromic v0.5244 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5244 UNC79 Zornitza Stark Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC79-related to Neurodevelopmental disorder (MONDO:0700092), UNC79-related
Intellectual disability syndromic and non-syndromic v0.5243 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC79-related to Neurodevelopmental disorder (MONDO:0700092), UNC79-related
Intellectual disability syndromic and non-syndromic v0.5243 UNC79 Zornitza Stark Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC79-related
Intellectual disability syndromic and non-syndromic v0.5242 NSUN6 Elena Savva Classified gene: NSUN6 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5242 NSUN6 Elena Savva Gene: nsun6 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5241 NSUN6 Elena Savva Marked gene: NSUN6 as ready
Intellectual disability syndromic and non-syndromic v0.5241 NSUN6 Elena Savva Gene: nsun6 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5241 UNC79 Elena Savva Classified gene: UNC79 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5241 UNC79 Elena Savva Gene: unc79 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5241 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Neurodevelopmental disorder (MONDO:0700092), UNC70-related to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Intellectual disability syndromic and non-syndromic v0.5240 UNC79 Elena Savva Classified gene: UNC79 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5240 UNC79 Elena Savva Gene: unc79 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5240 UNC79 Elena Savva Phenotypes for gene: UNC79 were changed from Complex neurodevelopmental disorder - MONDO:0100038 to Neurodevelopmental disorder (MONDO:0700092), UNC70-related
Intellectual disability syndromic and non-syndromic v0.5239 UNC79 Elena Savva Marked gene: UNC79 as ready
Intellectual disability syndromic and non-syndromic v0.5239 UNC79 Elena Savva Gene: unc79 has been removed from the panel.
Intellectual disability syndromic and non-syndromic v0.5239 NSUN6 Michelle Torres gene: NSUN6 was added
gene: NSUN6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: NSUN6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSUN6 were set to 37226891
Phenotypes for gene: NSUN6 were set to neurodevelopmental disorder MONDO:0700092, NSUN6-related
Review for gene: NSUN6 was set to AMBER
Added comment: Three unrelated consanguineous families with developmental delay, intellectual disability, motor delay, and behavioral anomalies. WES detected homozygous variants:
- p.(Leu9Glufs*3): even though authors say is is predicted to cause NMD, it actually is NMD escape. No further studies were performed. A deceased affected sibling and parents were NOT tested.
- p.(Asp323Asn): Shown to result in a misfolded protein. Methylation assay showed mutant could not catalyze m5C deposition in transcribed tRNACys and tRNAThr substrates in vitro. One of the parents and both unaffected siblings were shown to be carriers.
- p.(Glu441Profs*15): truncation (full protein is 470aa) which would result in loss of residues involved in recognition and methylation. Shown to result in a misfolded protein. Parents were shown carriers.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5239 UNC79 Krithika Murali edited their review of gene: UNC79: Changed phenotypes: Neurodevelopmental disorderMONDO:0700092
Intellectual disability syndromic and non-syndromic v0.5239 UNC79 Krithika Murali gene: UNC79 was added
gene: UNC79 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: UNC79 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UNC79 were set to PMID:37183800
Phenotypes for gene: UNC79 were set to Complex neurodevelopmental disorder - MONDO:0100038
Review for gene: UNC79 was set to AMBER
Added comment: PMID:37183800 Bayat et al 2023 report 6 unrelated patients with heterozygous NMD-predicted LoF variants in UNC79 - x1 canonical splice site variant, x5 nonsense/frameshift. 5 were confirmed de novo, 1 not identified in mother - father unavailable for testing. All variants absent in gnomAD and v2 pLI score for UNC79 is 1.

Patients with UNC79 variants were identified through GeneMatcher or an international network of Epilepsy and Genetics departments. x1 patient underwent duo exome sequencing, remaining had trio exome sequencing - no other causative variants identified.

Phenotypic features included:
- 4/6 autistic features
- 5/6 patients mild-moderate ID
- 4/6 behavioural issues (aggression, stereotypies)
- 4/6 epilepsy (focal to bilateral tonic-clonic seizures)
- 5/6 hypotonia

unc79 knockdown drosophila flies exhibited significantly higher rate of seizure-like behaviour than controls. unc79 haploinsufficiency shown to lead to significant reduction in protein levels of both unc79 and unc80 in mouse brains. Unc79 haploinsufficiency associated with deficiency in hippocampal-dependent learning and memory in mice.

Authors have reviewed their own evidence in relation to the gene-disease criteria detailed by Strande et al 2017 and note that their clinical and experimental data provides moderate-level evidence supporting the association between UNC79 and a neurodevelopment disorder including ASD.

Amber association favoured due to clinical phenotypic range reported between affected individuals and their lack of specificity.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5239 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5239 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5237 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5237 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Classified gene: POU3F2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Intellectual disability syndromic and non-syndromic v0.5238 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Intellectual disability syndromic and non-syndromic v0.5238 ACBD6 Elena Savva Marked gene: ACBD6 as ready
Intellectual disability syndromic and non-syndromic v0.5238 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5238 MCM6 Zornitza Stark Classified gene: MCM6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5238 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5238 ACBD6 Elena Savva Classified gene: ACBD6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5238 ACBD6 Elena Savva Gene: acbd6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5237 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Intellectual disability syndromic and non-syndromic v0.5237 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Intellectual disability syndromic and non-syndromic v0.5236 MCM6 Zornitza Stark Classified gene: MCM6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 MCM6 Zornitza Stark Classified gene: MCM6 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 MCM6 Zornitza Stark Gene: mcm6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5237 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Intellectual disability syndromic and non-syndromic v0.5237 POU3F2 Ain Roesley Phenotypes for gene: POU3F2 were changed from Autism spectrum disorder, NDD, and adolescent-onset obesity to Autism spectrum disorder, NDD, and adolescent-onset obesity; neurodevelopmental disorder MONDO:0700092, POU3F2-related
Intellectual disability syndromic and non-syndromic v0.5235 POU3F2 Ain Roesley Classified gene: POU3F2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5235 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Marked gene: POU3F2 as ready
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 U2AF2 Elena Savva Classified gene: U2AF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 U2AF2 Elena Savva Gene: u2af2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Classified gene: POU3F2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5236 POU3F2 Ain Roesley Gene: pou3f2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder, U2AF2-related (MONDO:0700092) to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Phenotypes for gene: U2AF2 were changed from Neurodevelopmental disorder MONDO:0700092, MMGT1-related to Neurodevelopmental disorder, U2AF2-related (MONDO:0700092)
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Publications for gene: U2AF2 were set to 33057194
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Classified gene: U2AF2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5235 U2AF2 Elena Savva Gene: u2af2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5234 ACBD6 Lucy Spencer gene: ACBD6 was added
gene: ACBD6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 36457943; 21937992; 35446914
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related
Review for gene: ACBD6 was set to GREEN
Added comment: PMID: 36457943
2 siblings with a neurodevelopmental disorder: severely delayed development, obesity, pancytopenia, diabetes, liver cirrhosis, intravertebral disc herniation, mild brain atrophy. Consanguineous family both siblings found to have a homozygous frameshift.

This paper also mentioned 3 other reported variants in 6 individuals (only 3 unrelated) all homozygous, 2 frameshift, 1 canonical splice. All reported to have a neurodevelopmental disorder, some with limited information but one family also has obesity, spasticity, and dysmorphism. PMIDs: 21937992, 35446914
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5234 POU3F2 Sarah Pantaleo commented on gene: POU3F2: Both loss of function and gain of function demonstrated
Intellectual disability syndromic and non-syndromic v0.5234 U2AF2 Paul De Fazio edited their review of gene: U2AF2: Changed publications: 34112922, 37092751, 36747105, 37134193
Intellectual disability syndromic and non-syndromic v0.5234 POU3F2 Sarah Pantaleo gene: POU3F2 was added
gene: POU3F2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU3F2 were set to PMID: 37207645
Phenotypes for gene: POU3F2 were set to Autism spectrum disorder, NDD, and adolescent-onset obesity
Penetrance for gene: POU3F2 were set to unknown
Mode of pathogenicity for gene: POU3F2 was set to Other
Review for gene: POU3F2 was set to GREEN
Added comment: We associate ultra-rare variants in POU3F2, encoding a central nervous system transcription factor, with syndromic obesity and neurodevelopment delay in 12 individuals. Demonstrate variant pathogenicity through in vitro analysis. Used exome sequencing, GeneMatcher and Genomics England 100,000 Genomes Project rare disease database.

Both truncating and missense variants in over 10 individuals sharing autism spectrum disorder, NDD, and adolescent-onset obesity (may have had other features eg. CAKUT in 2 individuals, diabetes in two) . Affected individuals presented with low-to-normal birth weight and infantile feeding difficulties but developed insulin resistance and hyperplasia during childhood. With the exception of an early truncating variant, the variants showed adequate nuclear translocation but overall disturbed DNA-binding ability and promoter activation.

Variants absent from population and clinical databases. Almost all constituted putatively non-inherited de novo variants (8/10).

Functional studies provide evidence for loss of function in eight and gain of function in one obesity-associated POU3F2 variant. One variant did not impact POU3F2-promoter activation, leaving the possibility for further path-mechanisms.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5234 U2AF2 Paul De Fazio edited their review of gene: U2AF2: Changed rating: GREEN; Changed phenotypes: Neurodevelopmental disorder, U2AF2-related (MONDO:0700092); Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5234 U2AF2 Paul De Fazio reviewed gene: U2AF2: Rating: ; Mode of pathogenicity: None; Publications: 34112922,37092751,36747105,37134193; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5234 MAP4K4 Zornitza Stark Phenotypes for gene: MAP4K4 were changed from to RASopathy, MONDO:0021060, MAP4K4-related
Intellectual disability syndromic and non-syndromic v0.5233 MAP4K4 Zornitza Stark Mode of inheritance for gene: MAP4K4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5233 MAP4K4 Zornitza Stark Mode of inheritance for gene: MAP4K4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5232 MAP4K4 Zornitza Stark Publications for gene: MAP4K4 were set to 37126546
Intellectual disability syndromic and non-syndromic v0.5232 MAP4K4 Zornitza Stark Publications for gene: MAP4K4 were set to
Intellectual disability syndromic and non-syndromic v0.5231 MAP4K4 Zornitza Stark Classified gene: MAP4K4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5231 MAP4K4 Zornitza Stark Gene: map4k4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5230 MAP4K4 Zornitza Stark commented on gene: MAP4K4: 26 individuals from 21 families reported with Rasopathy-like phenotype, comprising ID/DD, dysmorphic features and congenital anomalies.
Intellectual disability syndromic and non-syndromic v0.5230 MAP4K4 Zornitza Stark edited their review of gene: MAP4K4: Changed rating: GREEN; Changed publications: 37126546; Changed phenotypes: RASopathy, MONDO:0021060, MAP4K4-related; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5230 MCM6 Suliman Khan gene: MCM6 was added
gene: MCM6 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MCM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MCM6 were set to PMID: 37198333
Phenotypes for gene: MCM6 were set to Neurodevelopmental disorder, MONDO:0700092, MCM6-related
Review for gene: MCM6 was set to GREEN
Added comment: PMID: 37198333 reported 5 unrelated families with de novo variants in MCM6 gene. Two patients with the same missense variant p.(Cys158Tyr) in zinc finger domain presented with intra-uterine growth retardation, short stature, congenital microcephaly, endocrine features, developmental delay and urogenital anomalies.

In other three unrelated individuals different de novo missense variants were identified in the oligo nucleotide binding (OB)-fold domain. These patients had variable neurodevelopmental features including autism spectrum disorder, developmental delay, and epilepsy.

The clinical features and functional defects related to the zinc binding residue resembled those observed in syndromes related to other MCM components and DNA replication factors (Meier–Gorlin syndrome and Seckel syndrome), while de novo OB-fold domain missense variants were associated with more variable neurodevelopmental phenotypes (PMID: 37198333).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5230 TPR Zornitza Stark Phenotypes for gene: TPR were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related to Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Intellectual disability syndromic and non-syndromic v0.5229 TPR Zornitza Stark edited their review of gene: TPR: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 79, MIM# 620393
Intellectual disability syndromic and non-syndromic v0.5229 UNC13A Ain Roesley Phenotypes for gene: UNC13A were changed from Congenital myasthenia; dyskinesia; autism; developmental delay to Congenital myasthenia; dyskinesia; autism; developmental delay; neurodevelopmental disorder MONDO#0700092, UNC13A-related
Intellectual disability syndromic and non-syndromic v0.5229 UNC13A Ain Roesley Classified gene: UNC13A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5229 UNC13A Ain Roesley Gene: unc13a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5228 UNC13A Ain Roesley reviewed gene: UNC13A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder MONDO#0700092, UNC13A-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.5228 ZNF292 Michelle Torres reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 64, MIM#619188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5228 ESAM Zornitza Stark Phenotypes for gene: ESAM were changed from Neurodevelopmental disorder (MONDO#0700092), ESAM-related to Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371
Intellectual disability syndromic and non-syndromic v0.5227 ESAM Zornitza Stark reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with intracranial haemorrhage, seizures, and spasticity, MIM# 620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5227 SLITRK2 Zornitza Stark Phenotypes for gene: SLITRK2 were changed from Neurodevelopmental disorder, SLITRK2-related MONDO:0700092 to Intellectual developmental disorder, X-linked 111, MIM# 301107
Intellectual disability syndromic and non-syndromic v0.5226 SLITRK2 Zornitza Stark reviewed gene: SLITRK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 111, MIM# 301107; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5226 INTS11 Zornitza Stark Phenotypes for gene: INTS11 were changed from Global developmental delay; launguage delay; intellectual disability; impaired motor development; brain atrophy to intellectual disability, MONDO:0001071
Intellectual disability syndromic and non-syndromic v0.5225 LHX2 Zornitza Stark Marked gene: LHX2 as ready
Intellectual disability syndromic and non-syndromic v0.5225 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5225 LHX2 Zornitza Stark Publications for gene: LHX2 were set to PMID:
Intellectual disability syndromic and non-syndromic v0.5224 LHX2 Zornitza Stark Phenotypes for gene: LHX2 were changed from to Neurodevelopmental disorder (MONDO: 0700092)
Intellectual disability syndromic and non-syndromic v0.5223 LHX2 Zornitza Stark Classified gene: LHX2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5223 LHX2 Zornitza Stark Gene: lhx2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5222 CBX1 Zornitza Stark Marked gene: CBX1 as ready
Intellectual disability syndromic and non-syndromic v0.5222 CBX1 Zornitza Stark Gene: cbx1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5222 CNOT9 Zornitza Stark Marked gene: CNOT9 as ready
Intellectual disability syndromic and non-syndromic v0.5222 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5222 CNOT9 Zornitza Stark Mode of inheritance for gene: CNOT9 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5221 CNOT9 Zornitza Stark Classified gene: CNOT9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5221 CNOT9 Zornitza Stark Gene: cnot9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5220 LHX2 Manny Jacobs reviewed gene: LHX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37057675; Phenotypes: Neurodevelopmental disorder (MONDO: 0700092); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5220 CNOT9 Karina Sandoval edited their review of gene: CNOT9: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5220 CBX1 Seb Lunke Classified gene: CBX1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5220 CBX1 Seb Lunke Gene: cbx1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5219 LHX2 Manny Jacobs gene: LHX2 was added
gene: LHX2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LHX2 were set to PMID:
Intellectual disability syndromic and non-syndromic v0.5219 INTS11 Seb Lunke Marked gene: INTS11 as ready
Intellectual disability syndromic and non-syndromic v0.5219 INTS11 Seb Lunke Gene: ints11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5219 CNOT9 Karina Sandoval gene: CNOT9 was added
gene: CNOT9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CNOT9 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CNOT9 were set to PMID: 37092538
Phenotypes for gene: CNOT9 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: CNOT9 was set to GREEN
Added comment: 7 individuals with de novo variants. In silico predictions of functional relevance. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include.

Symptoms: Neuro dev disorder. ID, Epilepsy. All affected persons have DD/ID, with five of them showing seizures. Other symptoms include muscular hypotonia, facial dysmorphism, and behavioral abnormalities.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5219 CBX1 Daniel Flanagan gene: CBX1 was added
gene: CBX1 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: CBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CBX1 were set to PMID: 37087635
Phenotypes for gene: CBX1 were set to Neurodevelopmental disorder (MONDO#0700092), CBX1-related
Review for gene: CBX1 was set to GREEN
Added comment: Three different de novo missense variants identified in three unrelated individuals with developmental delay, hypotonia, autistic features, and variable dysmorphic features such as broad forehead and head circumference above average. Mutant mice displayed increased latency-to-peak response, suggesting the possibility of synaptic delay or myelination deficits. Functional studies confirmed the reduction of mutant HP1β binding to heterochromatin.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.5219 INTS11 Seb Lunke Classified gene: INTS11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5219 INTS11 Seb Lunke Gene: ints11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Classified gene: SRSF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5218 INTS11 Seb Lunke Classified gene: INTS11 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5218 INTS11 Seb Lunke Gene: ints11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Marked gene: SRSF1 as ready
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Classified gene: SRSF1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5218 SRSF1 Zornitza Stark Gene: srsf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5217 POLR1A Elena Savva Classified gene: POLR1A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5217 POLR1A Elena Savva Gene: polr1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 INTS11 Melanie Marty gene: INTS11 was added
gene: INTS11 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to PMID: 37054711
Phenotypes for gene: INTS11 were set to Global developmental delay; launguage delay; intellectual disability; impaired motor development; brain atrophy
Review for gene: INTS11 was set to GREEN
Added comment: PMID: 37054711 - 15 individuals from 10 unrelated families with bi-allelic variants in INTS11 with global developmental and language delay, intellectual disability, 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.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5216 SRSF1 Paul De Fazio edited their review of gene: SRSF1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5216 POLR1A Elena Savva Marked gene: POLR1A as ready
Intellectual disability syndromic and non-syndromic v0.5216 POLR1A Elena Savva Gene: polr1a has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 SRSF1 Paul De Fazio gene: SRSF1 was added
gene: SRSF1 was added to Intellectual disability syndromic and non-syndromic. 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, SRSF1-related MONDO:0700092
Review for gene: SRSF1 was set to GREEN
gene: SRSF1 was marked as current diagnostic
Added comment: 17 individuals from 16 families reported with mostly de novo variants. Variants were a mixture of missense, nonsense/frameshift (both NMD-predicted and not NMD-predicted) and microdeletions. In one family, only one parent was available for testing. In another family, 2 affected siblings had the variant but the variant was not identified in either parent suggesting germline mosaicism.

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. Episignature analysis (EpiSign) on patient DNA from blood showed a specific DNA methylation signature in patients with the variants classified pathogenic but not those classified VUS.

Phenotypes included mainly neurological abnormalities (mild to moderate ID/dev delay, motor delay, speech delay, and behavioural disorders) and facial dysmorphisms.

Other features included hypotonia (11/16), variable brain abnormalities on MRI (6/12), variable cardiac malformations (6/14). urogenital malformations e.g. hypospadias, cryptorchidism (6/13), scoliosis (5/17) and/or variable other skeletal abnormalities (10/17).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5216 POLR1A Elena Savva gene: POLR1A was added
gene: POLR1A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: POLR1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POLR1A were set to PMID: 37075751
Phenotypes for gene: POLR1A were set to Acrofacial dysostosis, Cincinnati type MIM#616462
Review for gene: POLR1A was set to GREEN
Added comment: PMID: 37075751 - >10 patients with developmental delay
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Marked gene: SLC30A9 as ready
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Classified gene: SLC30A9 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5216 SLC30A9 Zornitza Stark Gene: slc30a9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5215 SLC30A9 Lucy Spencer gene: SLC30A9 was added
gene: SLC30A9 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A9 were set to 37041080
Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome (MIM#617595)
Review for gene: SLC30A9 was set to GREEN
Added comment: PMID:37041080 - 2 families previously reported and this paper describes 4 more with biallelic SLC30A9 variants. Original 2 families: 6 affected members all hom for Ala350del, and 1 affected member chet for 2 frameshifts. 4 families from this paper: 2 families have the same homozygous missense (Gly418Val), family 3 has 4 affected sibs hom for Ala350del, family 4 1 affected chet for a frameshift and a synonymous. So 2 fams homs for Ala350del and 2 fams hom for Gly418Val.
All have Brik-Landau-Perez syndrome: all with ID, movement disorder and dystonia, and many with oculomotor apraxia, renal abnormalitie, ptosis, some had hearing impairment.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5215 GATAD2A Bryony Thompson Marked gene: GATAD2A as ready
Intellectual disability syndromic and non-syndromic v0.5215 GATAD2A Bryony Thompson Gene: gatad2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5215 GATAD2A Bryony Thompson Classified gene: GATAD2A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5215 GATAD2A Bryony Thompson Gene: gatad2a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5214 GATAD2A Bryony Thompson gene: GATAD2A was added
gene: GATAD2A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: GATAD2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2A were set to https://doi.org/10.1016/j.xhgg.2023.100198; 17565372
Phenotypes for gene: GATAD2A were set to Neurodevelopmental disorder, MONDO:0700092, GATAD2A-related
Review for gene: GATAD2A was set to GREEN
Added comment: https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5213 KDM5A Zornitza Stark Marked gene: KDM5A as ready
Intellectual disability syndromic and non-syndromic v0.5213 KDM5A Zornitza Stark Gene: kdm5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5213 KDM5A Zornitza Stark Classified gene: KDM5A as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5213 KDM5A Zornitza Stark Gene: kdm5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5212 KDM5A Zornitza Stark gene: KDM5A was added
gene: KDM5A was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KDM5A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDM5A were set to 21937992; 33350388
Phenotypes for gene: KDM5A were set to Neurodevelopmental disorder MONDO:0700092, KDM5A-related
Review for gene: KDM5A was set to GREEN
Added comment: 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.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5211 YWHAE Zornitza Stark Marked gene: YWHAE as ready
Intellectual disability syndromic and non-syndromic v0.5211 YWHAE Zornitza Stark Gene: ywhae has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5211 YWHAE Zornitza Stark Classified gene: YWHAE as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5211 YWHAE Zornitza Stark Gene: ywhae has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5210 DNM1 Zornitza Stark Phenotypes for gene: DNM1 were changed from Developmental and epileptic encephalopathy 31, OMIM:616346 to Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346; Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Intellectual disability syndromic and non-syndromic v0.5209 DNM1 Zornitza Stark edited their review of gene: DNM1: Changed phenotypes: Developmental and epileptic encephalopathy 31A, autosomal dominant, MIM# 616346, Developmental and epileptic encephalopathy 31B, autosomal recessive, MIM# 620352
Intellectual disability syndromic and non-syndromic v0.5209 RBSN Elena Savva commented on gene: RBSN
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Zornitza Stark Tag disputed tag was added to gene: DNAH14.
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Elena Savva Classified gene: DNAH14 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Elena Savva Gene: dnah14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Elena Savva Classified gene: DNAH14 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5209 DNAH14 Elena Savva Gene: dnah14 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5208 DNAH14 Elena Savva reviewed gene: DNAH14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5208 RFX7 Zornitza Stark Phenotypes for gene: RFX7 were changed from ID, ASD, ADHD to Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, MIM# 620330
Intellectual disability syndromic and non-syndromic v0.5207 MED11 Zornitza Stark Phenotypes for gene: MED11 were changed from neurodevelopmental disorder MONDO#0700092, MED11-related to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327
Intellectual disability syndromic and non-syndromic v0.5206 MED11 Zornitza Stark reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, MIM# 620327; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5206 WARS Zornitza Stark Phenotypes for gene: WARS were changed from Neurodevelopmental disorder (MONDO:0700092), WARS-related to Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317
Intellectual disability syndromic and non-syndromic v0.5205 WARS Zornitza Stark reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder withmicrocephaly and speech delay, with or without brain abnormalities,MIM# 620317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5205 C16orf62 Chirag Patel Classified gene: C16orf62 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5205 C16orf62 Chirag Patel Gene: c16orf62 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5204 C16orf62 Chirag Patel reviewed gene: C16orf62: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36113987; Phenotypes: Ritscher-Schinzel syndrome-3 (RTSC3), MIM#619135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5204 ROBO1 Zornitza Stark Phenotypes for gene: ROBO1 were changed from intellectual disability, MONDO:0001071 to Neurooculorenal syndrome, MIM# 620305
Intellectual disability syndromic and non-syndromic v0.5203 ROBO1 Zornitza Stark reviewed gene: ROBO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurooculorenal syndrome, MIM# 620305; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5203 ROBO1 Zornitza Stark Marked gene: ROBO1 as ready
Intellectual disability syndromic and non-syndromic v0.5203 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5203 ROBO1 Zornitza Stark Classified gene: ROBO1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5203 ROBO1 Zornitza Stark Gene: robo1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5202 CAMSAP1 Zornitza Stark Phenotypes for gene: CAMSAP1 were changed from lissencephaly spectrum disorders (MONDO:0018838), CAMSAP1-related to Cortical dysplasia, complex, with other brain malformations 12, MIM# 620316
Intellectual disability syndromic and non-syndromic v0.5201 CAMSAP1 Zornitza Stark reviewed gene: CAMSAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cortical dysplasia, complex, with other brain malformations 12, MIM# 620316; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5201 YWHAE Yetong Chen gene: YWHAE was added
gene: YWHAE was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: YWHAE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: YWHAE were set to 36999555
Phenotypes for gene: YWHAE were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: YWHAE was set to GREEN
Added comment: PMID 36999555 reports 6 patients with YWHAE variants (1 intragenic deletion and 5 large deletions encompassing YWHEA but not PAFAH1B1) who have mild to severe intellectual disability.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5201 CRIPT Zornitza Stark Marked gene: CRIPT as ready
Intellectual disability syndromic and non-syndromic v0.5201 CRIPT Zornitza Stark Gene: cript has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5201 CRIPT Zornitza Stark Classified gene: CRIPT as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5201 CRIPT Zornitza Stark Gene: cript has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5200 MKL2 Zornitza Stark Marked gene: MKL2 as ready
Intellectual disability syndromic and non-syndromic v0.5200 MKL2 Zornitza Stark Gene: mkl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5200 RNH1 Zornitza Stark Phenotypes for gene: RNH1 were changed from RNH1-related disorder to Neurodevelopmental disorder, MONDO:0700092, RNH1-related
Intellectual disability syndromic and non-syndromic v0.5199 RNH1 Zornitza Stark reviewed gene: RNH1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, RNH1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5199 RNH1 Seb Lunke Marked gene: RNH1 as ready
Intellectual disability syndromic and non-syndromic v0.5199 RNH1 Seb Lunke Gene: rnh1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5199 RNH1 Seb Lunke Classified gene: RNH1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5199 RNH1 Seb Lunke Gene: rnh1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5198 CRIPT Karina Sandoval commented on gene: CRIPT: PMID: 37013901 identified 6 individuals with Rothmund-Thomson syndrome characterised by poikiloderma, sparse hair, small stature, skeletal defects, cancer, cataracts, resembling features of premature aging. Two new variants identified and 4 were already published. 5 were hom, 1 was chet, all with different variants.
All CRIPT individuals fulfilled the diagnostic criteria for RTS, and additionally had neurodevelopmental delay and seizures.

CRIPT-deficient fibroblasts showed an unremarkable mitotic progression and unremarkable number of mitotic errors,

c.132del p.(Ala45Glyfs*82), hom
c.227G>A, p.(Cys76Tyr), hom
c.133_134insGG,p.(Ala45Glyfs*82),hom
c.141del p.(Phe47Leufs*84), hom
c.8G>A p.(Cys3Tyr), 1,331 bp del exon 1, chet
c.7_8del; p.(Cys3Argfs*4), hom
Intellectual disability syndromic and non-syndromic v0.5198 CRIPT Karina Sandoval gene: CRIPT was added
gene: CRIPT was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CRIPT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRIPT were set to PMID: 37013901
Phenotypes for gene: CRIPT were set to Short stature with microcephaly and distinctive facies (MIM#615789) : Rothmund-Thomson syndrome MONDO:0010002
Review for gene: CRIPT was set to GREEN
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5198 MKL2 Zornitza Stark Classified gene: MKL2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5198 MKL2 Zornitza Stark Gene: mkl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5197 SNAPC4 Zornitza Stark Marked gene: SNAPC4 as ready
Intellectual disability syndromic and non-syndromic v0.5197 SNAPC4 Zornitza Stark Gene: snapc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5197 SNAPC4 Zornitza Stark Classified gene: SNAPC4 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5197 SNAPC4 Zornitza Stark Gene: snapc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5196 SNAPC4 Ee Ming Wong changed review comment from: - Ten individuals from eight families with neurodevelopmental disorder found to be compound heterozygous for variants in SNAPC4
- Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice
- Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts
Sources: Literature; to: - Ten individuals from eight families with neurodevelopmental disorder found to be biallelic for variants in SNAPC4
- Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice
- Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5196 ESAM Seb Lunke Marked gene: ESAM as ready
Intellectual disability syndromic and non-syndromic v0.5196 ESAM Seb Lunke Gene: esam has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5196 ESAM Seb Lunke Classified gene: ESAM as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5196 ESAM Seb Lunke Gene: esam has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5195 RNH1 Krithika Murali edited their review of gene: RNH1: Changed rating: RED
Intellectual disability syndromic and non-syndromic v0.5195 SNAPC4 Ee Ming Wong gene: SNAPC4 was added
gene: SNAPC4 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SNAPC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNAPC4 were set to 36965478
Phenotypes for gene: SNAPC4 were set to Neurodevelopmental disorder (MONDO#0700092), SNAPC4-related
Review for gene: SNAPC4 was set to GREEN
gene: SNAPC4 was marked as current diagnostic
Added comment: - Ten individuals from eight families with neurodevelopmental disorder found to be compound heterozygous for variants in SNAPC4
- Identified variants included 6x missense, 1x nonsense, 1x frameshift and 6x splice
- Depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing, similarly observed in patient fibroblasts
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5195 MKL2 Dean Phelan gene: MKL2 was added
gene: MKL2 was added to Intellectual disability syndromic and non-syndromic. 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 disorder (MONDO:0700092), MKL2-related
Mode of pathogenicity for gene: MKL2 was set to Other
Review for gene: MKL2 was set to AMBER
Added comment: PMID: 37013900
- de novo missense variants in MKL2 (now known as MRTFB) were identified in two patients with mild dysmorphic features, intellectual disability, global developmental delay, speech apraxia, and impulse control issues. Functional studies in a Drosophila model suggest a gain of function disease mechanism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5195 RNH1 Krithika Murali gene: RNH1 was added
gene: RNH1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNH1 were set to PMID: 36935417
Phenotypes for gene: RNH1 were set to RNH1-related disorder
Review for gene: RNH1 was set to AMBER
Added comment: PMID: 36935417 report two siblings from a consanguineous Somali family with homozygous RNH1 splice site variant (c.615-2A>C) with congenital cataracts, global developmental delay, hypotonia, seizures (focal and generalised) and regression in the context of infection. RT-PCR and RNASeq of skeletal muscle supported exon 7 skipping with an in-frame deletion involving 57 amino acids with reduced expression on Western blot analysis.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5195 ESAM Chern Lim gene: ESAM was added
gene: ESAM was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESAM were set to 36996813
Phenotypes for gene: ESAM were set to Neurodevelopmental disorder (MONDO#0700092), ESAM-related
Review for gene: ESAM was set to GREEN
gene: ESAM was marked as current diagnostic
Added comment: PMID 36996813:
- Thirteen affected individuals, including four fetuses, from eight unrelated families, with homozygous loss-of-function-type variants in ESAM – 2 of the variants are frameshifts, 1x nonsense, 1x canonical splice.
- Affected individuals have 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 fetuses.
- One of the frameshift variant c.115del (p.Arg39Glyfs*33), was detected in six individuals from four unrelated families from the same geographic region in Turkey (southeastern Anatolia), suggesting a founder effect.
- The c.451+1G>A variant was detected in three individuals from two independent families with the same ethnic origin (Arab Bedouin)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5195 NCAPG2 Zornitza Stark Classified gene: NCAPG2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5195 NCAPG2 Zornitza Stark Gene: ncapg2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5195 NCAPG2 Zornitza Stark Classified gene: NCAPG2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5195 NCAPG2 Zornitza Stark Gene: ncapg2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5194 NCAPG2 Zornitza Stark reviewed gene: NCAPG2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Khan-Khan-Katsanis syndrome, MIM# 618460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5194 SLC31A1 Zornitza Stark Phenotypes for gene: SLC31A1 were changed from Neurodevelopmental disorder, SLC31A1-related (MONDO#0700092) to Neurodegeneration and seizures due to copper transport defect, MIM# 620306
Intellectual disability syndromic and non-syndromic v0.5193 SLC31A1 Zornitza Stark edited their review of gene: SLC31A1: Changed phenotypes: Neurodegeneration and seizures due to copper transport defect, MIM# 620306
Intellectual disability syndromic and non-syndromic v0.5193 SCN1B Sangavi Sivagnanasundram Deleted their review
Intellectual disability syndromic and non-syndromic v0.5193 SCN1B Sangavi Sivagnanasundram reviewed gene: SCN1B: Rating: AMBER; Mode of pathogenicity: None; Publications: 9697698, 17020904, 12011299; Phenotypes: Generalized epilepsy with febrile seizures plus, type 1 (MONDO:0018214, MIM 604233); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.5193 AGO1 Zornitza Stark Phenotypes for gene: AGO1 were changed from Intellectual disability; autism to Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, MIM# 620292
Intellectual disability syndromic and non-syndromic v0.5192 AGO1 Zornitza Stark edited their review of gene: AGO1: Changed phenotypes: Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, MIM# 620292
Intellectual disability syndromic and non-syndromic v0.5192 TAB2 Lucy Spencer gene: TAB2 was added
gene: TAB2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TAB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAB2 were set to 35971781
Phenotypes for gene: TAB2 were set to Congenital heart defects, multiple types, 2 MONDO:0014000
Review for gene: TAB2 was set to GREEN
Added comment: PMID: 35971781 - expansion of the phenotype, 14 patients with TAB2 variants 6 have dev delay and 4 are also listed as having ID along with other phenotype features associated with this gene.

Note- there is a previous review of this paper in the mendeilome as amber
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5192 UBE3C Zornitza Stark Phenotypes for gene: UBE3C were changed from Neurodevelopmental disorder, MONDO:0700092, UBE3C-related to Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities, MIM# 620270
Intellectual disability syndromic and non-syndromic v0.5191 UBE3C Zornitza Stark edited their review of gene: UBE3C: Changed phenotypes: Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities, MIM# 620270
Intellectual disability syndromic and non-syndromic v0.5191 HECTD4 Zornitza Stark Phenotypes for gene: HECTD4 were changed from Neurodevelopmental disorder, MONDO:0700092, HECTD4-related to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, MIM# 620250
Intellectual disability syndromic and non-syndromic v0.5190 HECTD4 Zornitza Stark edited their review of gene: HECTD4: Changed phenotypes: Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, MIM# 620250
Intellectual disability syndromic and non-syndromic v0.5190 Zornitza Stark removed gene:MTSS1 from the panel
Intellectual disability syndromic and non-syndromic v0.5189 DPYSL2 Zornitza Stark Marked gene: DPYSL2 as ready
Intellectual disability syndromic and non-syndromic v0.5189 DPYSL2 Zornitza Stark Gene: dpysl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5189 DPYSL2 Zornitza Stark Phenotypes for gene: DPYSL2 were changed from intellectual disability, MONDO:0001071; Aplasia/Hypoplasia of the corpus callosum, HP:0007370 to intellectual disability, MONDO:0001071, DPYSL2-related
Intellectual disability syndromic and non-syndromic v0.5188 DPYSL2 Zornitza Stark Classified gene: DPYSL2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5188 DPYSL2 Zornitza Stark Gene: dpysl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5187 CTR9 Zornitza Stark Publications for gene: CTR9 were set to PMID: 35499524
Intellectual disability syndromic and non-syndromic v0.5186 RBSN Zornitza Stark Marked gene: RBSN as ready
Intellectual disability syndromic and non-syndromic v0.5186 RBSN Zornitza Stark Gene: rbsn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5186 RBSN Zornitza Stark Classified gene: RBSN as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5186 RBSN Zornitza Stark Gene: rbsn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5185 YWHAZ Zornitza Stark Marked gene: YWHAZ as ready
Intellectual disability syndromic and non-syndromic v0.5185 YWHAZ Zornitza Stark Gene: ywhaz has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5185 YWHAZ Zornitza Stark Classified gene: YWHAZ as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.5185 YWHAZ Zornitza Stark Gene: ywhaz has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5184 YWHAZ Achchuthan Shanmugasundram gene: YWHAZ was added
gene: YWHAZ was added to Intellectual disability syndromic and non-syndromic. 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 syndromic and non-syndromic v0.5184 RRAS2 Elena Savva Classified gene: RRAS2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5184 RRAS2 Elena Savva Gene: rras2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5183 RRAS2 Elena Savva Marked gene: RRAS2 as ready
Intellectual disability syndromic and non-syndromic v0.5183 RRAS2 Elena Savva Gene: rras2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.5183 RRAS2 Elena Savva gene: RRAS2 was added
gene: RRAS2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RRAS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RRAS2 were set to PMID: 31130282; 31130285
Phenotypes for gene: RRAS2 were set to Noonan syndrome 12 MIM#618624
Mode of pathogenicity for gene: RRAS2 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: RRAS2 was set to AMBER
Added comment: Gene has an established GOF mechanism

PMID: 31130282 - 3/9 individuals had mild learning difficulties or mild GDD

PMID: 31130285 - 1/3 individuals had mild ID, 1/3 had severe ID, 1/3 normal
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5182 RBSN Achchuthan Shanmugasundram gene: RBSN was added
gene: RBSN was added to Intellectual disability syndromic and non-syndromic. 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: 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.

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.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5182 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 zebrafish also showed that knockout/ over-expression of CTR9 variants caused motor defects and enlargement of telencephalon (homologous to the mammalian cerebrum).
Intellectual disability syndromic and non-syndromic v0.5182 DPYSL2 Achchuthan Shanmugasundram gene: DPYSL2 was added
gene: DPYSL2 was added to Intellectual disability syndromic and non-syndromic. 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.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5182 CTR9 Achchuthan Shanmugasundram reviewed gene: CTR9: Rating: ; Mode of pathogenicity: None; Publications: 35717577; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.5182 AMOTL1 Seb Lunke Marked gene: AMOTL1 as ready
Intellectual disability syndromic and non-syndromic v0.5182 AMOTL1 Seb Lunke Gene: amotl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5182 AMOTL1 Seb Lunke Classified gene: AMOTL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5182 AMOTL1 Seb Lunke Gene: amotl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5181 AMOTL1 Lucy Spencer gene: AMOTL1 was added
gene: AMOTL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 36751037
Phenotypes for gene: AMOTL1 were set to Orofacial clefting syndrome, MONDO:0015335, AMOTL1-related
Review for gene: AMOTL1 was set to GREEN
Added comment: PMID: 36751037- 16 individuals from 12 families with orofacial clefting syndrome and het variants in AMOTL1. Many in 1 hotspot: 5 individuals from 3 families have R157C, 6 individuals from another 4 families have R157H, 1 has P160L, and another has Q161R. Out of this hostpaot- 1 with P368A, 1 with E507K, 1 with E579K. 7 are de novo. All but 2 have clefting, 7 are dysmorphic, 5 have hearing loss, 9 have CHD, 7 have tall stature, 6 have dev delay. Other features include liver disease, myopia, scoliosis and immune involvement.

Another 2 families have been previously reported (described in the panelapp review in mendeliome) with variants in this hotspot 1 has 2 individuals with R157C, the other has 1 individual with P160L. All hotspot are absent from gnomad v2.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5181 SLC35B2 Zornitza Stark Marked gene: SLC35B2 as ready
Intellectual disability syndromic and non-syndromic v0.5181 SLC35B2 Zornitza Stark Gene: slc35b2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5181 SLC35B2 Zornitza Stark Classified gene: SLC35B2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5181 SLC35B2 Zornitza Stark Gene: slc35b2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5180 SLC35B2 Zornitza Stark gene: SLC35B2 was added
gene: SLC35B2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC35B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35B2 were set to 35325049
Phenotypes for gene: SLC35B2 were set to Leukodystrophy, hypomyelinating, 26, with chondrodysplasia, MIM# 620269
Review for gene: SLC35B2 was set to AMBER
Added comment: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy. Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5179 EMC1 Achchuthan Shanmugasundram reviewed gene: EMC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35234901; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5179 ATG4D Zornitza Stark Marked gene: ATG4D as ready
Intellectual disability syndromic and non-syndromic v0.5179 ATG4D Zornitza Stark Gene: atg4d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5179 ATG4D Zornitza Stark Phenotypes for gene: ATG4D were changed from neurodevelopmental disorder; Abnormal facial shape to Neurodevelopmental disorder, MONDO:0700092, ATG4D-related
Intellectual disability syndromic and non-syndromic v0.5178 ATG4D Zornitza Stark Classified gene: ATG4D as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5178 ATG4D Zornitza Stark Gene: atg4d has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5177 ATG4D Zornitza Stark reviewed gene: ATG4D: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, ATG4D-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5177 ROBO1 Achchuthan Shanmugasundram gene: ROBO1 was added
gene: ROBO1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ROBO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROBO1 were set to 28286008; 30692597; 35227688; 35348658
Phenotypes for gene: ROBO1 were set to intellectual disability, MONDO:0001071
Review for gene: ROBO1 was set to GREEN
Added comment: 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.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5177 ATG4D Suliman Khan gene: ATG4D was added
gene: ATG4D was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATG4D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG4D were set to PMID: 36765070
Phenotypes for gene: ATG4D were set to neurodevelopmental disorder; Abnormal facial shape
Penetrance for gene: ATG4D were set to unknown
Review for gene: ATG4D was set to GREEN
Added comment: PMID: 36765070 reported three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment with a similar facial gestalt comprising almond-shaped eyes, depressed nasal bridge, and a prominent Cupid’s bow with variable disease severity and progression. NGS analysis revealed bi-allelic loss-of-function variants in ATG4D gene. Based on the clinical, bioinformatic, and functional data, the author concluded that bi-allelic loss-of-function variants in ATG4D contribute to the pathogenesis of syndromic neurodevelopmental disorder.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.5177 PPM1K Zornitza Stark Publications for gene: PPM1K were set to 23086801
Intellectual disability syndromic and non-syndromic v0.5176 PPM1K Zornitza Stark Classified gene: PPM1K as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5176 PPM1K Zornitza Stark Gene: ppm1k has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.5175 PPM1K Zornitza Stark edited their review of gene: PPM1K: Added comment: PMID: 36706222 reported a patient with MSUD with mild findings and elevated BCAA levels carrying a novel homozygous start-loss variant in PPM1K.; Changed rating: AMBER; Changed publications: 23086801, 36706222
Intellectual disability syndromic and non-syndromic v0.5175 RAB39B Zornitza Stark Marked gene: RAB39B as ready
Intellectual disability syndromic and non-syndromic v0.5175 RAB39B Zornitza Stark Gene: rab39b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5175 RAB39B Zornitza Stark Phenotypes for gene: RAB39B were changed from to Intellectual developmental disorder, X-linked 72, OMIM:300271; Waisman syndrome, OMIM:311510
Intellectual disability syndromic and non-syndromic v0.5174 RAB39B Zornitza Stark Publications for gene: RAB39B were set to
Intellectual disability syndromic and non-syndromic v0.5173 RAB39B Zornitza Stark Mode of inheritance for gene: RAB39B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.5172 JPH3 Zornitza Stark Phenotypes for gene: JPH3 were changed from Intellectual disability; dystonia to Neurodevelopmental disorder, MONDO:0700092, JPH3-related; Intellectual disability; dystonia
Intellectual disability syndromic and non-syndromic v0.5171 JPH3 Zornitza Stark Publications for gene: JPH3 were set to 33824468
Intellectual disability syndromic and non-syndromic v0.5170 JPH3 Zornitza Stark Mode of inheritance for gene: JPH3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.5169 JPH3 Zornitza Stark Classified gene: JPH3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.5169 JPH3 Zornitza Stark Gene: jph3 has been classified as Amber List (Moderate Evidence).