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Skeletal dysplasia

Gene: GNAS

Green List (high evidence)

GNAS (GNAS complex locus)
EnsemblGeneIds (GRCh38): ENSG00000087460
EnsemblGeneIds (GRCh37): ENSG00000087460
OMIM: 139320, Gene2Phenotype
GNAS is in 21 panels

5 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Acromelic dysplasias gp of SD, disorganized development of skeletal components gp of SD. Several cases. Also mutated in ACTH-independent macronodular adrenal hyperplasia 219080 IC;Pseudohypoparathyroidism Ic 612462;Pseudopseudohypoparathyroidism 612463; Review on behalf of Tracy Lester
Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

Phenotypes
McCune-Albright syndrome, somatic, mosaic 174800; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233

Eleanor Williams (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: GNAS; Initial rating suggestion: green
Created: 6 Mar 2019, 11:36 a.m.

Helen Brittain (Genomics England Curator)

Comment on mode of inheritance: For the phenotype pseudohypoparathyroidism, monoallelic and imprinted is the appropriate mode of inheritance as indicated. For the phenotype of McCune Albright syndrome, which includes polyostotic fibrous dysplasia, the mechanism is a post-zygotic variant leading to a somatic mosaic picture. The mode of inheritance is therefore still best matched to monoallelic, however depending on the level of mosaicism in the tissue tested, the proportion of alleles with the variant could vary considerably (from 0-50%) and therefore the ability to detect it.
Created: 11 Jul 2017, 4:16 p.m.

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve Abbs
Created: 27 Jul 2016, 9:36 a.m.
Comment on mode of inheritance: All monogenic except for ACTH-independent macronodular adrenal hyperplasia 219080 (isolated cases) & McCune-Albright syndrome, 174800 (somatic mosaic)
Created: 7 Jul 2016, 11:13 a.m.
Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)
Created: 21 Jun 2016, 12:49 p.m.

Ana Beleza (Bristol Regional Genetics Service)

Green List (high evidence)

Tier 1
Created: 17 Jun 2016, 8:04 a.m.

Mode of inheritance
Other - please specify in evaluation comments

Phenotypes
ACTH-independent macronodular adrenal hyperplasia 219080 IC ; McCune-Albright syndrome, somatic, mosaic 174800 ; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233; Pseudohypoparathyroidism Ic 612462; Pseudopseudohypoparathyroidism 612463

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Sources
  • NHS GMS
  • Expert Review Green
  • Emory Genetics Laboratory
Phenotypes
  • Pseudohypoparathyroidism Ia 103580
  • Pseudopseudohypoparathyroidism 612463
  • Osseous heteroplasia, progressive 166350
  • Pseudohypoparathyroidism Ib 603233
  • Pseudohypoparathyroidism Ic 612462
  • ACTH-independent macronodular adrenal hyperplasia 219080 IC
  • McCune-Albright syndrome, somatic, mosaic 174800
OMIM
139320
Clinvar variants
Variants in GNAS
Penetrance
Complete
Panels with this gene

History Filter Activity

6 May 2019, Gel status: 4

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Added phenotypes Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233; Osseous heteroplasia, progressive 166350; McCune-Albright syndrome, somatic, mosaic 174800 for gene: GNAS

6 Mar 2019, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to GNAS. Rating Changed from Green List (high evidence) to Green List (high evidence)

11 Jul 2017, Gel status: 4

Set Mode of Inheritance

Helen Brittain (Genomics England Curator)

Mode of inheritance for GNAS was changed to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

9 Aug 2016, Gel status: 4

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to version 1 9th August 2016

7 Jul 2016, Gel status: 4

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for GNAS was changed to Other - please specifiy in evaluation comments

7 Jul 2016, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for GNAS were set to ACTH-independent macronodular adrenal hyperplasia 219080 IC ; McCune-Albright syndrome, somatic, mosaic 174800 ; Osseous heteroplasia, progressive 166350; Pseudohypoparathyroidism Ia 103580; Pseudohypoparathyroidism Ib 603233; Pseudohypoparathyroidism Ic 612462; Pseudopseudohypoparathyroidism 612463

21 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

18 May 2016, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

GNAS was added to Unexplained skeletal dysplasiapanel. Source: Emory Genetics Laboratory GNAS was added to Unexplained skeletal dysplasiapanel. Source: Expert Review Red

18 May 2016, Gel status: 0

Added New Source

Sarah Leigh (Genomics England Curator)

GNAS was added to Unexplained skeletal dysplasiapanel. Sources:

18 May 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

GNAS was created by sleigh