Neurofibromatosis Type 1

Gene: GNAS

Green List (high evidence)

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

3 reviews

Helen Brittain (Genomics England Curator)

Comment on mode of inheritance: As mentioned in the review, the phenotype of McCune Albright syndrome includes café-au-lait patches and is caused by post-zygotic variants leading to a somatic mosaic picture. The mode of inheritance is therefore 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, 4:08 p.m.

Alice Gardham (Genomics England)

Green List (high evidence)

Mosaic post-zygotic somatic activating mutations in GNAS are known to cause McCune-Albright syndrome. This syndrome is associated with polyostotic fibrous dysplasia, cafe-au-lait patches and precocious puberty.
Created: 31 Oct 2016, 4:50 p.m.

Mode of inheritance
Other

Phenotypes
McCune-Albright syndrome, 174800

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Helen Savage (Congenica Ltd)

Red List (low evidence)

Some overlapping phenotypic features, as defined in the inclusion criteria, between Fanconi anaemia and Pseudohypoparathyroidism Ia.
Created: 29 Jan 2016, 2:18 p.m.

Phenotypes
Pseudohypoparathyroidism Ia

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • McCune-Albright syndrome, 174800
  • Pseudohypoparathyroidism Ia
Tags
mosaicism
OMIM
139320
Clinvar variants
Variants in GNAS
Penetrance
Complete
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

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, imprinted status unknown

21 Dec 2016, Gel status: 4

Set Phenotypes

Alice Gardham (Genomics England)

Phenotypes for GNAS were set to McCune-Albright syndrome, 174800; Pseudohypoparathyroidism Ia

14 Nov 2016, Gel status: 4

panel promoted to version 1

Alice Gardham (Genomics England)

Panel finalised 14th November 2016

3 Nov 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

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

2 Nov 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

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

2 Nov 2016, Gel status: 0

Approved Gene

Alice Gardham (Genomics England)

This proposed gene was validated and added to this panel

31 Oct 2016, Gel status: 0

Created

Alice Gardham (Genomics England)

GNAS was created by agardham

31 Oct 2016, Gel status: 0

Added New Source

Alice Gardham (Genomics England)

GNAS was added to Neurofibromatosis Type 1panel. Sources: UKGTN