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Intellectual disability

Gene: SPEN

Green List (high evidence)
SPEN (spen family transcriptional repressor)
EnsemblGeneIds (GRCh38): ENSG00000065526
EnsemblGeneIds (GRCh37): ENSG00000065526
OMIM: 613484, Gene2Phenotype
SPEN is in 3 panels

4 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 14 Mar 2022, 2:22 p.m. | Last Modified: 14 Mar 2022, 2:22 p.m.
Panel Version: 3.1519
Created: 14 Mar 2022, 2:22 p.m.
Last Modified: 14 Mar 2022, 2:22 p.m.
Panel version: 3.1519

Arina Puzriakova (Genomics England Curator)

Comment on list classification: There is now enough evidence to promote this gene to Green at the next review - sufficient cases (>20) with truncating SPEN variants and GDD/ID of relevant severity to this panel.
Created: 6 Apr 2021, 4:35 p.m. | Last Modified: 6 Apr 2021, 4:35 p.m.
Panel Version: 3.996
Created: 6 Apr 2021, 4:35 p.m.
Last Modified: 6 Apr 2021, 4:35 p.m.
Panel version: 3.996

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is not enough evidence to support a gene-disease association so this gene has been given an Amber rating.
Created: 4 Dec 2020, 3:09 p.m. | Last Modified: 4 Dec 2020, 3:09 p.m.
Panel Version: 3.594
Created: 4 Dec 2020, 3:09 p.m.
Last Modified: 4 Dec 2020, 3:09 p.m.
Panel version: 3.594

Zornitza Stark (Australian Genomics)

Green List (high evidence)

PMID: 33596411
- 34 individuals with truncating variants in SPEN reported, most are de novo variants.
- Clinical profile includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females.
- Authors showed haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females.
Created: 5 Mar 2021, 6:27 a.m. | Last Modified: 5 Mar 2021, 6:27 a.m.
Panel Version: 3.975
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 25 de novo variants (6 frameshift, 1 in-frame, 7 missense, 8 stopgain, 3 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided, hence Amber rating).
Sources: Literature
Created: 4 Nov 2020, 5:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 4 Nov 2020, 5:24 a.m.

Panel version: 3.975

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • Developmental disorders
OMIM
613484
Clinvar variants
Variants in SPEN
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Mar 2022, Gel status: 3

Removed Tag

Ivone Leong (Genomics England Curator)

Tag Q2_21_rating was removed from gene: SPEN.

14 Mar 2022, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Green was added to SPEN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

6 Apr 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: SPEN were set to 33057194

6 Apr 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: spen has been classified as Amber List (Moderate Evidence).

6 Apr 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: SPEN.

4 Dec 2020, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: spen has been classified as Amber List (Moderate Evidence).

4 Nov 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: SPEN was added gene: SPEN was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPEN were set to 33057194 Phenotypes for gene: SPEN were set to Developmental disorders Review for gene: SPEN was set to AMBER