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Primary immunodeficiency

Gene: DCLRE1B

Green List (high evidence)

DCLRE1B (DNA cross-link repair 1B)
EnsemblGeneIds (GRCh38): ENSG00000118655
EnsemblGeneIds (GRCh37): ENSG00000118655
OMIM: 609683, Gene2Phenotype
DCLRE1B is in 3 panels

6 reviews

Arina Puzriakova (Genomics England Curator)

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

Zornitza Stark (Australian Genomics)

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

Kimberly Gilmour (Great Ormond Street Hopsital)

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

Tracy Briggs (Manchester Genomic Medicine Centre)

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

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

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.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Hoyeraal-Hreidarsson syndrome
  • 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
  • Combined immunodeficiencies with associated or syndromic features
Tags
Q3_21_expert_review
OMIM
609683
Clinvar variants
Variants in DCLRE1B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Sep 2021, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_21_expert_review tag was added to gene: DCLRE1B.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to DCLRE1B.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to DCLRE1B.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to DCLRE1B.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene DCLRE1B were set to Hoyeraal-Hreidarsson syndrome, 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, Combined immunodeficiencies with associated or syndromic features

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to DCLRE1B. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to DCLRE1B. Panel: Primary immunodeficiency disorders

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: dclre1b has been classified as Green List (High Evidence).

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: dclre1b has been classified as Green List (High Evidence).

20 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: DCLRE1B were set to 20479256

20 Jun 2018, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: DCLRE1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to DCLRE1B. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to DCLRE1B. Panel: Primary immunodeficiency disorders Phenotypes for gene DCLRE1B were set to Hoyeraal-Hreidarsson syndrome

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene DCLRE1B were set to Hoyeraal-Hreidarsson syndrome

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

DCLRE1B was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

DCLRE1B was created by Louise Daugherty