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| Intellectual disability v9.322 | CDC42BPB | Arina Puzriakova Mode of inheritance for gene: CDC42BPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.321 | CDC42BPB | Arina Puzriakova Publications for gene: CDC42BPB were set to 32031333 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.320 | CDC42BPB | Arina Puzriakova Tag Q1_26_promote_green tag was added to gene: CDC42BPB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.303 | CDC42BPB | Ida Ertmanska changed review comment from: Comment on list classification: There are several individuals reported in literature with a neurodevelopmental syndrome. In a 2020 report of 14 patients, 12 individuals had syndromic DD and/or ID (PMID: 32031333). Since the initial report, several studies have linked the gene to a neurodevelopmental disorder, though clinical details are limited. Based on available evidence, this gene should be promoted to Green for Intellectual disability with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.; to: Comment on list classification: There are several individuals reported in literature with a neurodevelopmental syndrome. In a 2020 report of 14 patients, 12 individuals had syndromic DD and/or ID (PMID: 32031333). Since the initial report, several studies have linked the gene to a neurodevelopmental disorder and ASD, though clinical details are limited. Based on available evidence, this gene should be promoted to Green for Intellectual disability with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.303 | CDC42BPB | Ida Ertmanska edited their review of gene: CDC42BPB: Changed publications to: 28263302, 31785789, 35586607, 36344539 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.303 | CDC42BPB |
Ida Ertmanska changed review comment from: Further reports (few clinical details): PMID: 36344539, Al Kasbi et al., 2022 4 yo male with hypotonia, global developmental delays and seizures, who had two homozygous variants: homozygous frameshift p.Ala1314GlyfsTer35 in CDC42BPB and homozygous missense p.Phe1306Val in SCN10A. PMID: 35586607 French et al., 2022 Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'. PMID: 31785789 Turner et al., 2019 Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo: NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0 13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0 13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0 14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0 DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0 DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0 PMID: 28263302 Yuen et al., 2017 Reported a de novo frameshift deletion in exon 11 of the CDC42BPB gene (Chr14:103442072_103442075delCTTT) in an individual with autism spectrum disorder by trio genome sequencing (sample AU079605; Supplementary Table 4).; to: Further reports (few clinical details): PMID: 36344539, Al Kasbi et al., 2022 4 yo male with hypotonia, global developmental delays and seizures, who had two homozygous variants: homozygous frameshift p.Ala1314GlyfsTer35 in CDC42BPB and homozygous missense p.Phe1306Val in SCN10A. PMID: 35586607 French et al., 2022 Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'. PMID: 31785789 Turner et al., 2019 Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo: NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0 13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0 13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0 14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0 DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0 DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0 PMID: 28263302 Yuen et al., 2017 Reported a de novo frameshift deletion in exon 11 of the CDC42BPB gene (Chr14:103442072_103442075delCTTT) in an individual with autism spectrum disorder by trio genome sequencing (sample AU079605; Supplementary Table 4). CDC42BPB is included in G2P with limited confidence (monoallelic CDC42BPB-related neurodevelopmental disorder). It is rated Green on Intellectual disability syndromic and non-syndromic panel in PA Australia. |
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| Intellectual disability v9.303 | CDC42BPB |
Ida Ertmanska changed review comment from: Further reports (few clinical details): PMID: 35586607 French et al., 2022 Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'. PMID: 31785789 Turner et al., 2019 Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo: NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0 13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0 13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0 14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0 DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0 DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0; to: Further reports (few clinical details): PMID: 36344539, Al Kasbi et al., 2022 4 yo male with hypotonia, global developmental delays and seizures, who had two homozygous variants: homozygous frameshift p.Ala1314GlyfsTer35 in CDC42BPB and homozygous missense p.Phe1306Val in SCN10A. PMID: 35586607 French et al., 2022 Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'. PMID: 31785789 Turner et al., 2019 Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo: NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0 13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0 13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0 14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0 DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0 DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0 PMID: 28263302 Yuen et al., 2017 Reported a de novo frameshift deletion in exon 11 of the CDC42BPB gene (Chr14:103442072_103442075delCTTT) in an individual with autism spectrum disorder by trio genome sequencing (sample AU079605; Supplementary Table 4). |
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| Intellectual disability v9.303 | CDC42BPB | Ida Ertmanska edited their review of gene: CDC42BPB: Added comment: Comment on list classification: There are several individuals reported in literature with a neurodevelopmental syndrome. In a 2020 report of 14 patients, 12 individuals had syndromic DD and/or ID (PMID: 32031333). Since the initial report, several studies have linked the gene to a neurodevelopmental disorder, though clinical details are limited. Based on available evidence, this gene should be promoted to Green for Intellectual disability with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.279 | CDC42BPB |
Ida Ertmanska changed review comment from: Further reports: PMID: 35586607 French et al., 2022 Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'. PMID: 31785789 Turner et al., 2019 Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo: NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0 13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0 13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0 14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0 DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0 DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0; to: Further reports (few clinical details): PMID: 35586607 French et al., 2022 Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'. PMID: 31785789 Turner et al., 2019 Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo: NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0 13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0 13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0 14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0 DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0 DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0 |
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| Intellectual disability v9.279 | CDC42BPB | Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype accessed 24th Feb 2026. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.279 | CDC42BPB | Ida Ertmanska Phenotypes for gene: CDC42BPB were changed from CDC42BPB-related Neurodevelopmental Disorder; Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality to Chilton-Okur-Chung neurodevelopmental syndrome, OMIM:619841; Chilton-Okur-Chung neurodevelopmental syndrome, MONDO:0859239 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v9.278 | CDC42BPB | Ida Ertmanska reviewed gene: CDC42BPB: Rating: AMBER; Mode of pathogenicity: None; Publications: 31785789, 35586607; Phenotypes: Chilton-Okur-Chung neurodevelopmental syndrome, OMIM:619841; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.89 | CDC42BPB | Sarah Leigh Classified gene: CDC42BPB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.89 | CDC42BPB | Sarah Leigh Gene: cdc42bpb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.88 | CDC42BPB | Sarah Leigh changed review comment from: Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene. At least 12 variants reported in 14 unrelated cases of CDC42BPB-related Neurodevelopmental Disorder. intellectual disability was apparent in 7/12 cases and at least 5 of these cases were de novo.; to: Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene. At least 12 variants reported in 14 unrelated cases of CDC42BPB-related Neurodevelopmental Disorder. Intellectual disability was apparent in 7/12 cases and at least 5 of these cases were de novo. However, only two of these cases did not have additional genetic changes reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.88 | CDC42BPB | Sarah Leigh Classified gene: CDC42BPB as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.88 | CDC42BPB | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM and as possible Gen2Phen gene. At least 12 variants reported in 14 unrelated cases of CDC42BPB-related Neurodevelopmental Disorder. intellectual disability was apparent in 7/12 cases and at least 5 of these cases were de novo. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.88 | CDC42BPB | Sarah Leigh Gene: cdc42bpb has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.87 | CDC42BPB | Sarah Leigh Added comment: Comment on phenotypes: CDC42BPB-related Neurodevelopmental Disorder is assigned by Gen2Phen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.87 | CDC42BPB | Sarah Leigh Phenotypes for gene: CDC42BPB were changed from Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality to CDC42BPB-related Neurodevelopmental Disorder; Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.35 | CDC42BPB |
Konstantinos Varvagiannis gene: CDC42BPB was added gene: CDC42BPB was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CDC42BPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CDC42BPB were set to 32031333 Phenotypes for gene: CDC42BPB were set to Central hypotonia; Global developmental delay; Intellectual disability; Seizures; Autistic behavior; Behavioral abnormality Penetrance for gene: CDC42BPB were set to unknown Review for gene: CDC42BPB was set to GREEN Added comment: Chilton et al (2020 - PMID: 32031333) report on 14 individuals with missense and loss-of-function CDC42BPB variants. Features included hypotonia (8/11), DD (12/13 - the 14th was a fetus), ID (7/13), ASD (8/12), clinical seizures (in 3 - a 4th had abnormal EEG without seizures), behavioral abnormalities. Variable non-specific dysmorphic features were reported in some (sparse hair being the most frequent - 4/8). Additional features were observed in few (=<4) incl. cryptorchidism, ophthalmological issues, constipation, kidney abnormalities, micropenis, etc. All individuals had non-diagnostic prior genetic testing (incl. CMA, FMR1, MECP2, Angelman/Prader-Willi methylation studies, autism gene panel - suggesting relevance to the current panel) or metabolic testing. Variants were identified following clinical exome sequencing with Sanger confirmation. Most occurred as de novo events (11/14) while inheritance was not available for few (3/14). Missense variants did not display (particular) clustering. Almost all variants were absent from gnomAD and were predicted to be deleterious in silico (among others almost all had CADD scores >25). As the authors comment, CDC42BPB encodes myotonic dystrophy-related Cdc42-binding kinase β (MRCKβ) a serine/threonine protein kinase playing a role in regulation of cytoskeletal reorganization and cell migration in nonmuscle cells (through phosporylation of MLC2). Previous studies have demonstrated that it is ubiquitously expressed with prenatal brain expression. The gene appears to be intolerant to pLoF (pLI of 1) as well as to missense variants (Z-score of 3.66). CDC42BPB is a downstream effector of CDC42. Mutations of the latter cause Takenouchi-Kosaki syndrome with DD/ID and some further overlapping features (with CDC42BPB-associated phenotypes). Homozygous Cdc42bpb KO in mouse appears to be nonviable (MGI:2136459). Loss of gek in the eyes of Drosophila results in disrupted growth cone targeting to the lamina (gek is the fly CDC42BPB ortholog). Please consider inclusion with amber / green rating in the ID panel (>=4 relevant individuals / variants) and other panels (e.g. for epilepsy, ASD). Sources: Literature |
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