Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: OAS1
Thomas Magg et al. identified four de novo heterozygous OAS1 gain-of-function variants in six patients with a polymorphic autoinflammatory immunodeficiency characterized by recurrent fever, dermatitis, inflammatory bowel disease, pulmonary alveolar proteinosis, and hypogammaglobulinemia.Created: 22 Jun 2021, 11:02 a.m. | Last Modified: 22 Jun 2021, 11:02 a.m.
Panel Version: 2.434
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
recurrent fever; dermatitis; inflammatory bowel disease; pulmonary alveolar proteinosis; hypogammaglobulinemia.
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
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:17 a.m.
Panel Version: 2.529
Additional publication identified by Boaz Palterer (PMID:34145065) supports the inclusion of this gene as Green on this panel. There are now at least 4 different gain-of-function heterozygous variants in the OAS1 gene identified in 8 unrelated families with 10 affected individuals (P5 in PMID:34145065 and C-II-1 in PMID:29455859 refer to the same individual).Created: 29 Jun 2021, 11:12 a.m. | Last Modified: 29 Jun 2021, 11:12 a.m.
Panel Version: 2.437
Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).Created: 20 Oct 2020, 2:41 p.m. | Last Modified: 20 Oct 2020, 2:41 p.m.
Panel Version: 2.337
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Comment on list classification: Upgraded rating from Amber to Green following advice from Helen Brittain (Genomics England Clinical Team): There appear to be three unrelated families with variants and hypogammaglobulinaemia. I think this is a relevant phenotype for immune dysfunction.Created: 18 May 2020, 8:26 a.m. | Last Modified: 18 May 2020, 8:26 a.m.
Panel Version: 2.169
Comment on list classification: Updated from Red to Amber, awaiting clinical review.Created: 29 Apr 2020, 8:24 p.m. | Last Modified: 29 Apr 2020, 8:24 p.m.
Panel Version: 2.138
PMID:29455859 (Cho et al. 2018) performed WES in a family with Pulmonary alveolar proteinosis (PAP) with hypogammaglobulinemia. They identified a heterozygous missense variant in OAS1 in 3 affected siblings. The mother showed mosaicism, suggesting AD inheritance from the maternal side. The authors identify 2 additional OAS1 heterozygous de novo variants in 2 unrelated individuals with PAP + hypogammaglobulinemia.Created: 29 Apr 2020, 8:23 p.m. | Last Modified: 29 Apr 2020, 8:23 p.m.
Panel Version: 2.137
Five individuals from three unrelated families including 3 sibs where the variant was present at mosaic level in one parent.Created: 11 Apr 2020, 4:50 a.m. | Last Modified: 11 Apr 2020, 4:50 a.m.
Panel Version: 2.51
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinemia
Publications
Variants in this GENE are reported as part of current diagnostic practice
Added publication referenced by IUIS december 2019 updateCreated: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
Publications
Phenotypes for gene: OAS1 were changed from Autoinflammatory Disorders; Pulmonary alveolar proteinosis; Recurrent fever; Dermatitis; Inflammatory bowel disease; Hypogammaglobulinemia to Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemia, OMIM:618042
Tag gene-checked was removed from gene: OAS1.
Tag gene-checked tag was added to gene: OAS1.
Tag for-review was removed from gene: OAS1.
Source Expert Review Green was added to OAS1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: OAS1 were changed from Autoinflammatory Disorders; Pulmonary alveolar proteinosis, skin rash; OAS1 GOF to Autoinflammatory Disorders; Pulmonary alveolar proteinosis; Recurrent fever; Dermatitis; Inflammatory bowel disease; Hypogammaglobulinemia
Mode of pathogenicity for gene: OAS1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: OAS1 were set to 32086639; 29455859; 32048120
Gene: oas1 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: OAS1.
Gene: oas1 has been classified as Green List (High Evidence).
Gene: oas1 has been classified as Amber List (Moderate Evidence).
Publications for gene OAS1 were updated from 32048120; 32086639 to 32086639; 29455859; 32048120
gene: OAS1 was added gene: OAS1 was added to Primary immunodeficiency. Sources: IUIS Classification December 2019 Mode of inheritance for gene: OAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: OAS1 were set to 32048120; 32086639 Phenotypes for gene: OAS1 were set to Autoinflammatory Disorders; Pulmonary alveolar proteinosis, skin rash; OAS1 GOF