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| Intellectual disability - microarray and sequencing v4.94 | DPYSL2 | Achchuthan Shanmugasundram Classified gene: DPYSL2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v4.94 | DPYSL2 | Achchuthan Shanmugasundram Gene: dpysl2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v4.94 | DPYSL2 | Achchuthan Shanmugasundram Classified gene: DPYSL2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v4.94 | DPYSL2 | Achchuthan Shanmugasundram Gene: dpysl2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v4.93 | DPYSL2 |
Achchuthan Shanmugasundram changed review comment from: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients. PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus. It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype. Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability. Sources: Literature; to: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients. PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus. It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype. Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability. This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype. Sources: Literature |
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| Intellectual disability - microarray and sequencing v4.93 | DPYSL2 |
Achchuthan Shanmugasundram gene: DPYSL2 was added gene: DPYSL2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: DPYSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DPYSL2 were set to 27249678; 35861646 Phenotypes for gene: DPYSL2 were set to intellectual disability, MONDO:0001071; Aplasia/Hypoplasia of the corpus callosum, HP:0007370 Review for gene: DPYSL2 was set to AMBER Added comment: This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients. PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus. It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype. Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability. Sources: Literature |
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| Intellectual disability - microarray and sequencing v3.1519 | DPYSL5 | Ivone Leong Tag Q3_21_rating was removed from gene: DPYSL5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1519 | DPYS | Ivone Leong Tag Q2_21_expert_review was removed from gene: DPYS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1519 | DPYSL5 | Sarah Leigh commented on gene: DPYSL5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1519 | DPYS | Sarah Leigh commented on gene: DPYS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1519 | DPYSL5 |
Ivone Leong Source Expert Review Green was added to DPYSL5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v3.1519 | DPYS |
Ivone Leong Source Expert Review Green was added to DPYS. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v3.1198 | DPYSL5 | Ivone Leong Tag Q3_21_rating tag was added to gene: DPYSL5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1198 | DPYSL5 | Ivone Leong Classified gene: DPYSL5 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1198 | DPYSL5 | Ivone Leong Gene: dpysl5 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1069 | DPYSL5 |
Zornitza Stark gene: DPYSL5 was added gene: DPYSL5 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: DPYSL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DPYSL5 were set to 33894126 Phenotypes for gene: DPYSL5 were set to Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities Review for gene: DPYSL5 was set to GREEN gene: DPYSL5 was marked as current diagnostic Added comment: Nine individuals with brain malformations, including corpus callosum agenesis and/or posterior fossa abnormalities, associated with variable degrees of intellectual disability. The recurrent de novo p.Glu41Lys was found in eight unrelated patients, and a p.Gly47Arg variant was identified in one individual from the first family reported with Ritscher-Schinzel syndrome. Both impaired DPYSL5 function on dendritic outgrowth regulation by preventing the formation of the ternary complex with MAP2 and βIII-tubulin, ultimately leading to abnormal brain development. Sources: Literature |
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| Intellectual disability - microarray and sequencing v3.1029 | DPYS | Arina Puzriakova Tag Q2_21_expert_review tag was added to gene: DPYS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1029 | DPYS | Arina Puzriakova Publications for gene: DPYS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1028 | DPYS | Arina Puzriakova Classified gene: DPYS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1028 | DPYS | Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Overall variable clinical presentation, even including asymptomatic subjects. However, DD and/or ID have been reported in multiple published cases (PMIDs: 9266350; 17383919; 20362666; 27604308; 26771602; 29054612). Sufficient unrelated cases (>3) to rate Green but will seek opinion from the GMS expert group due to highly variable penetrance of this phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1028 | DPYS | Arina Puzriakova Gene: dpys has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1027 | DPYS | Arina Puzriakova Phenotypes for gene: DPYS were changed from Dihydropyrimidinuria, MIM#222748 to Dihydropyrimidinuria, OMIM:222748 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1003 | DPYS |
Zornitza Stark gene: DPYS was added gene: DPYS was added to Intellectual disability. Sources: Expert Review Mode of inheritance for gene: DPYS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DPYS were set to Dihydropyrimidinuria, MIM#222748 Review for gene: DPYS was set to GREEN gene: DPYS was marked as current diagnostic Added comment: Highly variable phenotype, but many have ID. Sources: Expert Review |
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