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Intellectual disability

Gene: SETD1A

Amber List (moderate evidence)

SETD1A (SET domain containing 1A)
EnsemblGeneIds (GRCh38): ENSG00000099381
EnsemblGeneIds (GRCh37): ENSG00000099381
OMIM: 611052, Gene2Phenotype
SETD1A is in 4 panels

2 reviews

David Curtis (UCL)

Green List (high evidence)

Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. https://www.nature.com/articles/nn.4267
PMID: 26974950
LOF variants were seen only in subjects with schizophrenia without marked physical abnormalities and in subjects described as having developmental delay within a sample of children with diverse, severe developmental disorders. A further subject had mental retardation, short stature, mild facial dysmorphology and EEG abnormalities and was also diagnosed with delusional disorder and unspecified psychosis at 15 years of age. An additional subject had epilepsy and personality disorder.
Thus it seems that LOF variants in SETD1A can produce developmental disorder with intellectual disability as part of the phenotype or can result in other neuropsychiatric diagnoses including schizophrenia without severe intellectual disability.
Created: 5 Feb 2018, 2:56 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Schizophrenia; developmental disorder

Publications

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

added watchgene tag
Created: 26 Feb 2018, 4:36 p.m.
Comment on list classification: Changed status from Red to Amber after internal clinical review.
An external reviewer suggested a Green rating, however during internal review there was some concern rating the gene Green in the ID panel in view of the presence (albeit small numbers; 2) in ExAC, and it is unclear if the initial presentation was with Schizophrenia in the majority. So the level of ID may not be great enough from the reported cases to date to warrant inclusion, however it was noted that LoF variants were found in 4 cases from an ID cohort, so the Amber rating was suggested until further reports.
Created: 26 Feb 2018, 4:27 p.m.
Probable gene in Developmental Disorders Genotype-Phenotype Database (DDG2P) with the attributed disease intellectual disability PMID:28135719. Singh et al (2016) PMID: 26974950 analyzed whole genome sequences of 4,264 schizophrenia cases and identified rare loss of function variants in SETD1A and risk of schizophrenia and other neurodevelopmental phenotypes, one being intellectual disability. There were four patients noted with schizophrenia and delayed developmental milestones, however it was noted that the study design focused on schizophrenia and not ID, so could not confirm that the variants were specifically associated with the cognitive features.
Created: 18 Dec 2017, 3:39 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Intellectual disability

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Expert Review Amber
Phenotypes
  • Schizophrenia
  • developmental disorder
  • Intellectual disability
Tags
watchlist
OMIM
611052
Clinvar variants
Variants in SETD1A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

26 Feb 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for SETD1A were set to Schizophrenia; developmental disorder; Intellectual disability

26 Feb 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

26 Feb 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

5 Jan 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SETD1A was added to Intellectual disability panel. Sources: Expert Review Red

5 Jan 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

SETD1A was created by Ellen McDonagh