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Intellectual disability v9.303 WDR47 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: WDR47.
Intellectual disability v9.299 WDR47 Arina Puzriakova reviewed gene: WDR47: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.298 WDR47 Arina Puzriakova Source NHS GMS was added to WDR47.
Source Expert Review Green was added to WDR47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.206 WDR47 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WDR47.
Intellectual disability v8.53 WDR47 Achchuthan Shanmugasundram Phenotypes for gene: WDR47 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.52 WDR47 Achchuthan Shanmugasundram edited their review of gene: WDR47: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v8.52 WDR47 Achchuthan Shanmugasundram Classified gene: WDR47 as Amber List (moderate evidence)
Intellectual disability v8.52 WDR47 Achchuthan Shanmugasundram Gene: wdr47 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.51 WDR47 Achchuthan Shanmugasundram Classified gene: WDR47 as Amber List (moderate evidence)
Intellectual disability v8.51 WDR47 Achchuthan Shanmugasundram Gene: wdr47 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.50 WDR47 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: WDR47.
Intellectual disability v8.50 WDR47 Achchuthan Shanmugasundram Publications for gene: WDR47 were set to 39609633
Intellectual disability v8.49 WDR47 Achchuthan Shanmugasundram gene: WDR47 was added
gene: WDR47 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: WDR47 was set to GREEN
Added comment: PMID:39609633 reported seven patients from five unrelated families with either homozygous or compound heterozygous variants in WDR47 gene. They all presented with a complex neurodevelopmental syndrome comprising corpus callosum dysgenesis, microcephaly, intellectual disability and epilepsy. Profound intellectual disability was present in four of five reported families.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v3.1519 WDR4 Ivone Leong Tag Q2_21_rating was removed from gene: WDR4.
Intellectual disability v3.1519 WDR4 Sarah Leigh commented on gene: WDR4
Intellectual disability v3.1519 WDR4 Ivone Leong Source Expert Review Green was added to WDR4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v3.1240 WDR45B Arina Puzriakova Phenotypes for gene: WDR45B were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977 to Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, OMIM:617977
Intellectual disability v3.1062 WDR4 Ivone Leong reviewed gene: WDR4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.1062 WDR4 Ivone Leong Phenotypes for gene: WDR4 were changed from Primordial dwarfism; motor and speech delay; intellectual disability; global developmental delay. to Galloway-Mowat syndrome 6, OMIM:61834; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM:618347
Intellectual disability v3.1061 WDR4 Ivone Leong Tag Q2_21_rating tag was added to gene: WDR4.
Intellectual disability v3.1061 WDR4 Ivone Leong Publications for gene: WDR4 were set to 29597095; 26416026
Intellectual disability v3.67 WDR45B Rebecca Foulger Phenotypes for gene: WDR45B were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977
Intellectual disability v3.67 WDR45B Rebecca Foulger Publications for gene: WDR45B were set to 21937992; 28503735
Intellectual disability v2.784 BRSK2 Konstantinos Varvagiannis gene: BRSK2 was added
gene: BRSK2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: BRSK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BRSK2 were set to https://doi.org/10.1016/j.ajhg.2019.02.002
Phenotypes for gene: BRSK2 were set to Global developmental delay; Intellectual disability; Autism; Behavioral abnormality
Penetrance for gene: BRSK2 were set to unknown
Review for gene: BRSK2 was set to GREEN
gene: BRSK2 was marked as current diagnostic
Added comment: Hiatt et al. (2019 - https://doi.org/10.1016/j.ajhg.2019.02.002) report on 9 individuals, each with private heterozygous BRSK2 variant.

Features included among others speech or motor delay, ID (8/9), ASD and variable behavioral anomalies.

6 variants predicted LoF (stopgain, frameshift or affecting splice-site) while 3 additional ones were missense (2 in the protein kinase domain and 1 in the kinase-associated 1 domain). In 6 individuals the variant had occurred as a de novo event while for 3 others parental samples were unavailable. Given the unknown inheritance, a single variant did not meet sufficient ACMG criteria to be classified as P/LP.

All variants had in silico predictions supporting a deleterious effect and were absent from bravo database and gnomAD, where the gene appears to be relatively intolerant to protein-altering variation.

As the authors note BRSK2 encodes a serine/threonine protein kinase involved in axonogenesis and polarization of cortical neurons. Although Brsk2- (or Brsk1-) knockout mice appear to be healthy and fertile, double knockouts for these genes resulted in pups with decreased spontaneous movement, poor response to tactile stimulation that died shortly after birth. In mice Brsk2 (and Brsk1) expression is restricted to the nervous system (PMID cited by the authors: 15705853) while in humans this gene is most highly expressed in brain (PMID cited: 23715323 - GTEx project).

BRSK2 has been shown to interact with other neurodevelopmental genes eg. TSC2, PTEN, WDR45.

Within the cohort of individuals studied, there was statistically significant enrichment for de novo BRSK2 variants when compared to the estimated backround mutation rate.

Two further BRSK2 de novo protein-altering variants were previously reported in individuals with neurodevelopmental disorders (Iossifov et al. - PMID: 25363768 and DDD study - PMID: 28135719) although the missense variant in the latter study is also present in gnomAD database.

BRSK2 is not associated with any phenotype in OMIM, nor in G2P.
The gene is included in gene panels for ID offered by some diagnostic laboratories (eg. among those participating in the study).

As a result, this gene can be considered for inclusion in the ID panel as green (or amber).
Sources: Literature
Intellectual disability v2.468 WDR45B Louise Daugherty Source Victorian Clinical Genetics Services was added to WDR45B.
Intellectual disability WDR4 Louise Daugherty classified WDR4 as Amber List (moderate evidence)
Intellectual disability WDR4 Ellen McDonagh commented on WDR4
Intellectual disability WDR4 Ellen McDonagh edited their review of WDR4
Intellectual disability WDR4 Ellen McDonagh Added gene to panel
Intellectual disability WDR45 BRIDGE consortium edited their review of WDR45
Intellectual disability WDR45 BRIDGE consortium edited their review of WDR45
Intellectual disability WDR45 BRIDGE consortium reviewed WDR45
Intellectual disability WDR45B Sarah Leigh edited their review of WDR45B
Intellectual disability WDR45B Sarah Leigh classified WDR45B as green
Intellectual disability WDR45B Sarah Leigh commented on WDR45B