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Intellectual disability

Gene: SMARCA1

Amber List (moderate evidence)
SMARCA1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1)
EnsemblGeneIds (GRCh38): ENSG00000102038
EnsemblGeneIds (GRCh37): ENSG00000102038
OMIM: 300012, Gene2Phenotype
SMARCA1 is in 1 panel

4 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

SMARCA1 variants have not been associated with a condition in OMIM and have been assigned a limited association with X-linked intellectual disability (MONDO:0100284) in ClinGen. At total of nine SMARCA1 variants have been reported in unrelated cases with intellectual disability and other neurological features (PMID: 26539891; 26740508; 27479843; 27457812; 33057194; 40316778). Five of these variants are missense and four are nonsense or frameshifting, suggesting a pathogenic effect. Inheritance from the unaffected mother was proved in at least three of the cases (PMID: 27457812; 40316778). All but of one of the cases were males, the female case had a de novo SMARCA1 missense variant (PMID: 26740508). The recent report in PMID: 40316778 of two unrelated cases with intellectual disability may contribute to a change in the Limited classification of SMARCA1 in ClinGen.
Created: 7 May 2025, 10:05 a.m. | Last Modified: 7 May 2025, 10:05 a.m.
Panel Version: 9.16

Phenotypes
X-linked intellectual disability, MONDO:0100284

Publications

Created: 7 May 2025, 10:05 a.m.
Last Modified: 7 May 2025, 10:05 a.m.
Panel version: 9.16

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

1 case only from PMID:26539891: Patient BAB4453 presented with microcephaly, spasticity, and ID. He also had very similar dysmorphic features similar to those seen in Coffin-Siris syndrome. He was found to have a hemizygous null variant in the SMARCA1 gene (NM_003069: c.C7T, p.Q3X). Insufficient evidence for inclusion on a diagnostic ID panel.
Created: 31 Oct 2017, 9:24 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Created: 31 Oct 2017, 9:24 a.m.

Panel version: Imported from Intellectual disability update Oct 2017 panel version 0.4

Louise Daugherty (Genomics England Curator)

Comment on mode of inheritance: Changed from Monallelic to X-linked. ClinGen groups X-linked disorder with autosomal dominant https://search.clinicalgenome.org/kb/gene-validity/5479, the mode of inheritance for SMARCA1 should be X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Created: 25 Sep 2017, 1:18 p.m.
Created: 25 Sep 2017, 1:18 p.m.

Panel version: 1.427

Ellen McDonagh (Genomics England Curator)

Comment on list classification: One case study.
Created: 18 Jul 2017, 2:48 p.m.
This gene and information was sourced from the ClinGen Gene Validity Curations. For the full report and publications, see the ClinGen Gene Validity Curation for each gene here: https://search.clinicalgenome.org/kb/gene-validity. It was rated limited by the ClinGen CALCULATED CLASSIFICATION (06/14/2016) and moderate by the ClinGen expert curation (11/15/2016).
Created: 18 Jul 2017, 2:45 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Coffin-Siris Syndrome; ORPHA1465

Publications

Created: 18 Jul 2017, 2:45 p.m.

Panel version: 1.163

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Amber
  • Other
Phenotypes
  • X-linked intellectual disability, MONDO:0100284
Tags
Q2_25_ promote_green
OMIM
300012
Clinvar variants
Variants in SMARCA1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

7 May 2025, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SMARCA1 were changed from Coffin-Siris Syndrome; ORPHA1465 to X-linked intellectual disability, MONDO:0100284

7 May 2025, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_25_ promote_green tag was added to gene: SMARCA1.

7 May 2025, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: smarca1 has been classified as Amber List (Moderate Evidence).

6 May 2025, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SMARCA1 were set to 26539891; 26740508

12 Mar 2018, Gel status: 1

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.

25 Sep 2017, Gel status: 1

Set Mode of Inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for SMARCA1 was changed to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

18 Jul 2017, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

18 Jul 2017, Gel status: 0

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for SMARCA1 were set to 26539891; 26740508

18 Jul 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

SMARCA1 was created by ellenmcdonagh

18 Jul 2017, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

SMARCA1 was added to Intellectual disabilitypanel. Sources: Other