Intellectual disability - microarray and sequencing
Gene: SETD1B
A recent publication (PMID: 32546566) reports four additional patients with de novo SETD1B variants: a splice-site variant c.5589+1G>A (p.?), nonsense variants c.2932C>T: p.(Gln978Ter) and c.3964C>T p.(Gln1322Ter), and a missense variant c.5833T>C p.(Phe1945Leu). All individuals demonstrate a shared phenotype, including global developmental delay (two individuals with moderate ID), speech impairment, and seizures.Created: 30 Jul 2020, 12:11 p.m. | Last Modified: 30 Jul 2020, 12:11 p.m.
Panel Version: 3.209
Comment on list classification: Promoted from amber to green as there is now sufficient evidence to support a gene-disease association, based on submitted reviews.Created: 24 Jun 2019, 10:11 a.m. | Last Modified: 24 Jun 2019, 10:11 a.m.
Panel Version: 2.880
A recent publication (PMID: 31110234) reported on a third case of a Japanese patient with a de novo frameshift variant in SETD1B with intellectual disability, developmental delay and myoclonic seizures. Previously, there were 2 unrelated cases of Japanese patients with de novo variants in this gene and 4 unrelated cases of patients with de novo 12q24.3 deletion encompassing SETD1B. All SNV variants are different.Created: 24 Jun 2019, 10:06 a.m. | Last Modified: 24 Jun 2019, 10:06 a.m.
Panel Version: 2.878
Publications
Apart from the patients by Hiraide et al. (PMID: 29322246) there seems to be no other relevant individual published, at least with clinical details.
In Decipher, patient 368813 has a de novo frameshift variant (p.Leu742ProfsTer100) which has been submitted as likely pathogenic, associated with delayed speech and language development, mild ID, ASD, and abnormal eating behavior and associated growth abnormality (overweight).
There are also 2 further individuals with DDD research variants in this gene and abnormality of the nervous system [1 missense, 1 frameshift - https://decipher.sanger.ac.uk/gene/SETD1B#variants/SETD1B/ddd-research-variant-overlap].
Additional patients with de novo variants and developmental disorder, ID, ASD appear in the denovo-db:
http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=SETD1b
ClinVar has no relevant submissions (of SNVs).
SETD1B is not associated with any phenotype in OMIM, nor in G2P.
This gene is included in gene panels for ID offered by diagnostic laboratories (incl. Radboudumc).Created: 20 Dec 2018, 9:28 a.m.
Variants in this GENE are reported as part of current diagnostic practice
As a result of watchlist tag audit the watchlist tag was removed from SETD1B- this is now a green gene with sufficient evidence/reviewCreated: 13 Jan 2020, 4:11 p.m. | Last Modified: 13 Jan 2020, 4:11 p.m.
Panel Version: 3.0
added watchlist tagCreated: 27 Jul 2018, 3:31 p.m.
Comment on list classification: Rated gene as Amber based on current information in the literature, external expert review and internal clinical reviewCreated: 27 Jul 2018, 3:31 p.m.
After internal clinical review it as decided to leave this gene as rated Amber and not promote to Green, this is in view of the deletion cases being broader and containing several other genes. Recommend adding watch list tag.Created: 27 Jul 2018, 3:29 p.m.
Past onto clinical team for further review and consideration of upgrading gene to Green. Hiraide T et al. (2018) PMID: 29322246 summarised the clinical features of SETD1B variants, including two unrelated cases reported in this publication that had missense de novo variants they also reviewed previous reports of four previously reported individuals with a de novo 12q24.3 deletion encompassing SETD1B (Baple et al. 2010; Labonne et al. 2016; Palumbo et al. 2015; Qiao et al. 2013). Study suggests that SETD1B aberration is likely to be the core defect in 12q24.3 deletion syndrome.Created: 24 Jul 2018, 4:33 p.m.
Comment on publications: In addition to the publication describing denovo missense vars PMID:29322246, added publications describing microdeletions Labonne et al. (2016) PMID: 27106595 and Palumbo (2015) PMID: 25428890Created: 24 Jul 2018, 3:42 p.m.
Comment on phenotypes: added phenotypes from publicationsCreated: 24 Jul 2018, 3:39 p.m.
Comment on list classification: New amber gene added by external expert review, who notes Two individuals from unrelated families with de novo variants , ID is part of the phenotype.Created: 24 Jul 2018, 3:21 p.m.
Two individuals from unrelated families with de novo variants in this gene reported in the literature. Consider inclusion as Amber in anticipation of further cases.Created: 22 Jun 2018, 2:35 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: SETD1B were set to 29322246; 27106595; 25428890; 31110234
Phenotypes for gene: SETD1B were changed from Epilepsy, developmental delay, intellectual disability, autistic behavior and craniofacial dysmorphic features to Intellectual developmental disorder with seizures and language delay, OMIM:619000; Intellectual developmental disorder with seizures and language delay, MONDO:0033559
Tag watchlist was removed from gene: SETD1B.
Gene: setd1b has been classified as Green List (High Evidence).
Publications for gene: SETD1B were set to 29322246; 27106595; 25428890
Source Victorian Clinical Genetics Services was added to SETD1B.
Gene: setd1b has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SETD1B were set to Epilepsy, developmental delay, intellectual disability, autistic behavior and craniofacial dysmorphic features
Publications for gene: SETD1B were set to 29322246; 27106595; 25428890
Phenotypes for gene: SETD1B were set to Intellectual disability, epilepsy, autism; epilepsy, developmental delay, intellectual disabilities, autistic behavior and craniofacial dysmorphic features
Gene: setd1b has been classified as Amber List (Moderate Evidence).
Gene: setd1b has been classified as Amber List (Moderate Evidence).
SETD1B was added to Intellectual disability panel. Sources: Literature
SETD1B was created by Zornitza Stark