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Intellectual disability

Gene: GNAS

Green List (high evidence)
GNAS (GNAS complex locus)
EnsemblGeneIds (GRCh38): ENSG00000087460
EnsemblGeneIds (GRCh37): ENSG00000087460
OMIM: 139320, Gene2Phenotype
GNAS is in 19 panels

5 reviews

Sarah Leigh (Genomics England Curator)

Comment on mode of inheritance: Disease causing variants in the GNAS locus have differing expression panels. Pseudohypothyroidism Ia & Ic are all caused by GNAS variants arising in the maternal alleles, therefore, the mode of inheritance (MOI) for GNAS in these conditions should be monoallelic maternally imprinted. Pseudopseudohypoparathyroidism, OMIM:612463 is associated with variants in the paternal alleles therefore, the mode of inheritance for GNAS in this condition should be monoallelic paternally imprinted. Because intellectual disability is seen in these phenotypes, the MOI has been set to monoallelic, imprinted status unknown.
Created: 13 Oct 2022, 2:22 p.m. | Last Modified: 13 Oct 2022, 2:22 p.m.
Panel Version: 3.1745
Created: 13 Oct 2022, 2:22 p.m.
Last Modified: 13 Oct 2022, 2:22 p.m.
Panel version: 3.1745

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known;in_UKGTN_v12 . Main mutation mechanism : Activating; Loss of function
Created: 27 Jul 2017, 6:21 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; gilissen_2014_known; sfari_20150206; UKGTN_v12; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Activating; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:34 p.m.

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

Publications

Mode of pathogenicity

Created: 2 Aug 2017, 6:37 p.m.

Panel version: 1.354

Ellen McDonagh (Genomics England Curator)

Comment on mode of inheritance: Changed from 'other' to monoallelic, to allow variants to be tiered within this gene. Loss of function mutations on the maternal allele cause pseudohypoparathyroidism type Ia; loss of function mutations on the paternal allele cause pseudopseudohypoparathyroidism, so the imprinted allele can change.
Created: 9 May 2017, 2:43 p.m.
Added 'mosaicism' tag to reflect reviewer's comment.
Created: 5 Apr 2017, 6:08 a.m.
Created: 5 Apr 2017, 6:08 a.m.

Panel version: 1.118

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:55 a.m.

Panel version: 0.306

Caroline Wright (Sanger)

Green List (high evidence)

Mechanism: Mosaic
Created: 16 Nov 2015, 11:25 a.m.

Mode of inheritance
Other - please specify in evaluation comments

Phenotypes
ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA (AIMAH)

Publications

  • 0

Created: 16 Nov 2015, 11:25 a.m.

Panel version: 0

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Pseudohypoparathyroidism Ia, OMIM:103580
  • pseudohypoparathyroidism type 1A, MONDO:0007078
  • Pseudohypoparathyroidism Ic, OMIM:612462
  • pseudohypoparathyroidism type 1C, MONDO:0012911
  • Pseudopseudohypoparathyroidism, OMIM:612463
  • pseudopseudohypoparathyroidism, MONDO:0012912
Tags
mosaicism
OMIM
139320
Clinvar variants
Variants in GNAS
Penetrance
Complete
Panels with this gene

History Filter Activity

13 Oct 2022, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: GNAS were changed from Pseudohypoparathyroidism Ia, 103580McCune-Albright syndrome, 174800Pseudohypoparathyroidism Ic, 612462Osseous heteroplasia, progressive, 166350Pseudohypoparathyroidism Ib, 603233Prolonged bleeding time, brachydactyly and mental retardationAcromegaly, 102200Pseudopseudohypoparathyroidism, 612463Prolonged bleeding time, brachydactyly, and mental retardationACTH-independent macronodular adrenal hyperplasia, 219080; ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA (AIMAH) to Pseudohypoparathyroidism Ia, OMIM:103580; pseudohypoparathyroidism type 1A, MONDO:0007078; Pseudohypoparathyroidism Ic, OMIM:612462; pseudohypoparathyroidism type 1C, MONDO:0012911; Pseudopseudohypoparathyroidism, OMIM:612463; pseudopseudohypoparathyroidism, MONDO:0012912

13 Oct 2022, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: GNAS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

28 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to GNAS.

12 Mar 2018, Gel status: 3

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.

9 May 2017, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for GNAS was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

GNAS was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene GNAS was set to Other - please specify in evaluation comments

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

GNAS was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen