Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: UBA1
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red.Created: 2 Feb 2023, 11:32 a.m. | Last Modified: 2 Feb 2023, 11:32 a.m.
Panel Version: 3.4
Comment on list classification: The rating of this gene has been left as red for now, as it is a somatic variant. Advice will be sought as to the best rating. It is also being reviewed on the 'Autoinflammatory disorders' wet lab panel by the Test Evaluation Working Group.Created: 25 May 2022, 10:14 a.m. | Last Modified: 25 May 2022, 10:14 a.m.
Panel Version: 2.550
NRAS and KRAS SOMATIC variants are included as Amber in this panelCreated: 21 Sep 2022, 4:51 p.m. | Last Modified: 21 Sep 2022, 4:51 p.m.
Panel Version: 2.577
Multiple patients described in the literature. Significant proportion of patients (see PMID: 34048852) have somatic mutation load in blood >=50% , so this WOULD be picked up for at least a fraction of patients with standard genomic tests.Created: 12 Nov 2021, 7:14 p.m. | Last Modified: 12 Nov 2021, 7:14 p.m.
Panel Version: 2.485
Mode of inheritance
Other
Phenotypes
VEXAS autoinflammatory condition
Publications
Comment on list classification: New gene added by Zornitza Stark. Relevant phenotype but rating Red as this panel is not appropriate for somatic variant detection due to the coverage and therefore variants are unlikely to be picked up by our current pipeline (added 'somatic' tag).Created: 24 Nov 2020, 12:05 p.m. | Last Modified: 24 Nov 2020, 12:05 p.m.
Panel Version: 2.374
25 men reported with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation, and an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopaenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis.
Sources: LiteratureCreated: 4 Nov 2020, 9:50 a.m.
Mode of inheritance
Other
Phenotypes
Autoinflammatory disease, adult onset; VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic)
Publications
Tag Q2_22_rating was removed from gene: UBA1. Tag Q2_22_expert_review was removed from gene: UBA1. Tag Q2_22_NHS_review was removed from gene: UBA1.
Gene: uba1 has been classified as Red List (Low Evidence).
Tag Q2_22_expert_review tag was added to gene: UBA1. Tag Q2_22_NHS_review tag was added to gene: UBA1.
Tag to_be_confirmed_NHSE was removed from gene: UBA1.
Tag to_be_confirmed_NHSE tag was added to gene: UBA1. Tag Q2_22_rating tag was added to gene: UBA1.
Gene: uba1 has been classified as Red List (Low Evidence).
Gene: uba1 has been removed from the panel.
Phenotypes for gene: UBA1 were changed from Autoinflammatory disease, adult onset; VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) to VEXAS syndrome, somatic, OMIM:301054
Tag somatic tag was added to gene: UBA1.
gene: UBA1 was added gene: UBA1 was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: UBA1 was set to Other Publications for gene: UBA1 were set to 33108101 Phenotypes for gene: UBA1 were set to Autoinflammatory disease, adult onset; VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) Review for gene: UBA1 was set to GREEN