Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: DCLRE1B

I don't know

The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Added the Q3_21_rating tag to make it clear that it is the rating of this gene that is being assessed.

Created: 6 Oct 2022, 2:19 p.m. | Last Modified: 6 Oct 2022, 2:19 p.m.

Panel Version: 2.577

Added 'to_be_confirmed_NHSE' tag as demotion of this gene requires further discussion

Created: 18 Feb 2022, 5:16 p.m. | Last Modified: 18 Feb 2022, 5:16 p.m.

Panel Version: 2.527

DCLRE1B will be flagged for GMS expert review to re-evaluate the evidence pertaining to this gene. The rating was previously set to Green based on consensus by the Immunology Specialist Group - however the evidence is based on a single published case of Hoyeraal-Hreidarsson syndrome (PMID: 20479256) where a short transcript of DCLRE1B was discovered following targeted RT-PCR amplification of factors involved in telomere protection. Sequencing of DCLRE1B did not reveal any variants, and so authors postulated that the alternative transcript resulted from alteration of an uncharacterised element (also see Red review by Zornitza Stark, 19 Aug 2021). This gene is currently not associated with any phenotype in OMIM or G2P.

Created: 14 Sep 2021, 12:24 p.m. | Last Modified: 14 Sep 2021, 12:24 p.m.

Panel Version: 2.462

Publications

• 20479256

Red List (low evidence)

One individual with Hoyeraal-Hreidarsson syndrome reported with shortened transcript in DCLRE1B of the patient’s cells; not seen in controls or other HH patients.

Shortened transcript identified caused by intra-exonic splice of exon 4 leading to out-of-frame deletion causing premature stop codon (denoted splice variant “Apollo-Δ”)

No molecular origin of splice variant could be identified and only linked to HH is by this one reported patient and the known DCLRE1B (SNM1B) role in telomere protection.

Created: 19 Aug 2021, 4:30 a.m. | Last Modified: 19 Aug 2021, 4:30 a.m.

Panel Version: 2.458

Mode of inheritance
Unknown

Phenotypes
Dyskeratosis congenita and Hoyeraal-Hreidarsson (HH) syndrome

Publications

• 20479256
• 21647296

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

Green List (high evidence)

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): DCLRE1B/ SNM1/APOLLO .PanelApp HGNC gene symbol check: DCLRE1B . IUIS Disease: AR-DKC due to DCLRE1B deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Variable, .IUIS Other affected cells: N/A. IUIS Associated features: Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: DyskeratosIs Congenita (DKC), Myelodysplasia, Short Telomeres

Created: 2 Jul 2018, 10:35 a.m.

Comment on list classification: Changed Amber to Green from external review comment and added publications to support gene-disease association

Created: 20 Jun 2018, 9:47 p.m.

Comment on publications: added publication to support gene-disease association. SNM1B is a synonym gene symbol for DCLRE1B

Created: 20 Jun 2018, 9:45 p.m.

Comment on mode of inheritance: added MOI from IUIS

Created: 20 Jun 2018, 9:44 p.m.

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 20 Apr 2018, 12:25 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: APOLLO (snm1b def), PanelApp HGNC gene symbol check: DCLRE1B, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Dyskeratosis congenita / Hoyeraal-Hreidarsson syndrome

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: DCLRE1B, GRID_Gene_Symbol: DCLRE1B, GRID_Transcript_ENS_Community submitted: ENST00000369563, GRID_Transcript_RefSeq: NM_001319946.1, GRID_Transcript_ENS_used_on_Production: ENST00000369563

Created: 17 Apr 2018, 12:12 p.m.