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Primary immunodeficiency

Gene: DNASE1L3

Amber List (moderate evidence)

DNASE1L3 (deoxyribonuclease 1 like 3)
EnsemblGeneIds (GRCh38): ENSG00000163687
EnsemblGeneIds (GRCh37): ENSG00000163687
OMIM: 602244, Gene2Phenotype
DNASE1L3 is in 2 panels

7 reviews

Arina Puzriakova (Genomics England Curator)

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, 3:22 p.m. | Last Modified: 20 Oct 2020, 3:22 p.m.
Panel Version: 2.348

Catherine Snow (Genomics England)

Comment on list classification: Identified by expert review as Green. PMID: 30008451 reports a SLE patient with (c.289_290delAC/p.Thr97Ilefs*2) in DNASE1L3 in 1 patient. This variant had previously been reported in PMID: 23666765 for Hypocomplementemic Urticarial Vasculitis (HUVs) - Systemic lupus erythematosus (SLE) develops in >50% of patients with HUVS
Created: 28 Apr 2020, 5:52 p.m. | Last Modified: 28 Apr 2020, 5:52 p.m.
Panel Version: 2.133

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Six consanguineous families with paediatric-onset SLE reported initially, same homozygous mutation (founder); additional family identified in literature with different homozygous frameshift.
Created: 10 Apr 2020, 6:17 a.m. | Last Modified: 10 Apr 2020, 6:17 a.m.
Panel Version: 2.51

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Systemic lupus erythematosus 16, MIM# 614420

Publications

Kimberly Gilmour (Great Ormond Street Hopsital)

I don't know

agree with all the Amber genes
Created: 25 Sep 2019, 1:49 p.m. | Last Modified: 25 Sep 2019, 1:49 p.m.
Panel Version: 1.115

Tracy Briggs (Manchester Genomic Medicine Centre)

I don't know

The amber genes are covered on our targeted exome, we feel that these should be covered in the testing
Created: 25 Sep 2019, 1:44 p.m. | Last Modified: 25 Sep 2019, 1:44 p.m.
Panel Version: 1.114

Louise Daugherty (Genomics England Curator)

I don't know

Added publication referenced by IUIS december 2019 update
Created: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
SLE in Arab families (6 but consistent with founder effect)
Created: 26 Sep 2019, 3:52 p.m. | Last Modified: 26 Sep 2019, 3:52 p.m.
Panel Version: 1.130
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 only enough evidence to rate this gene Amber.
Created: 25 Sep 2019, 3 p.m. | Last Modified: 25 Sep 2019, 3 p.m.
Panel Version: 1.116
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 only enough evidence to rate this gene Amber
Created: 25 Sep 2019, 3 p.m. | Last Modified: 25 Sep 2019, 3 p.m.
Panel Version: 1.116
Comment on list classification: Amber rating not Green rating. From clinical review it was noted that this is a single variant with a founder effect so amber rating as there
is no confirmatory evidence that the variant/gene is causative (other cases or functional data). Also not sure that the SLE phenotype is the best fit for the PID panel
Created: 6 Jul 2018, 4:09 p.m.
added deletions tag. Although a deletion, it is small (1bp) so is reportable with current pipeline
Created: 6 Jul 2018, 10:56 a.m.
Comment on list classification: Changed Amber to Green.
Created: 6 Jul 2018, 10:54 a.m.
added founder effect tag
Created: 6 Jul 2018, 10:52 a.m.
From PMID Al-Mayouf et al. (2011) PMID: 22019780 identified homozygosity for a 1-bp deletion (643delT) in the DNASE1L3 gene in 6 affected members of consanguineous Arab families with systemic lupus erythematosus. The mutation segregated perfectly with the disease state in a strictly mendelian, fully penetrant, and autosomal recessive fashion in all 6 families, and was not found in 192 ethnically matched controls. Haplotype analysis confirmed this to be a founder mutation. In lymphoblast cell lines from 2 patients, no DNASE1L3 transcript was detected, and tissue culture studies demonstrated that mutant DNASE1L3 completely lacks DNase activity.
Created: 6 Jul 2018, 10:52 a.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): DNASE1L3 .PanelApp HGNC gene symbol check: DNASE1L3 . IUIS Disease: DNASE1L3 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Systemic lupus erythematosus, lupus nephritis, hypocomplementemic urticarial vasculitis. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Autoimmunity with or without Lymphoproliferation
Created: 6 Jul 2018, 10:48 a.m.

Publications

Sophie Hambleton (Newcastle University)

I don't know

one variant described, 6 families
Created: 29 Jun 2018, 8:18 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
familial early-onset SLE

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • IUIS Classification December 2019
  • North West GLH
  • London North GLH
  • NHS GMS
  • IUIS Classification February 2018
Phenotypes
  • Systemic lupus erythematosus 16, 614420
  • Diseases of Immune Dysregulation
  • Autoinflammatory Disorders
  • Systemic lupus erythematosus, lupus nephritis, hypocomplementemic urticarial vasculitis
  • familial early-onset SLE
Tags
deletions founder-effect for-review
OMIM
602244
Clinvar variants
Variants in DNASE1L3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: dnase1l3 has been classified as Amber List (Moderate Evidence).

20 Oct 2020, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: DNASE1L3.

28 Apr 2020, Gel status: 3

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: dnase1l3 has been classified as Green List (High Evidence).

28 Feb 2020, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene DNASE1L3 were updated from 32048120; 22019780; 32086639 to 27821515; 23666765; 22019780; 32086639; 32048120

28 Feb 2020, Gel status: 2

Added New Source, Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Source IUIS Classification December 2019 was added to DNASE1L3. Added phenotypes Systemic lupus erythematosus, lupus nephritis, hypocomplementemic urticarial vasculitis; Autoinflammatory Disorders for gene: DNASE1L3 Publications for gene DNASE1L3 were updated from 22019780 to 32048120; 22019780; 32086639

17 Sep 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to DNASE1L3.

17 Sep 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to DNASE1L3.

17 Sep 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to DNASE1L3.

12 Jul 2018, Gel status: 2

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.

6 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: dnase1l3 has been classified as Amber List (Moderate Evidence).

6 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: dnase1l3 has been classified as Amber List (Moderate Evidence).

6 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: dnase1l3 has been classified as Green List (High Evidence).

6 Jul 2018, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: DNASE1L3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

6 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: DNASE1L3 were set to 22019780

6 Jul 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: DNASE1L3 were set to Systemic lupus erythematosus 16, 614420; familial early-onset SLE; Systemic lupus erythematosus, lupus nephritis, hypocomplementemic urticarial vasculitis; Diseases of Immune Dysregulation

6 Jul 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: DNASE1L3 were set to familial early-onset SLE; Systemic lupus erythematosus, lupus nephritis, hypocomplementemic urticarial vasculitis; Diseases of Immune Dysregulation

6 Jul 2018, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: DNASE1L3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

6 Jul 2018, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: DNASE1L3 was changed from to BIALLELIC, autosomal or pseudoautosomal

1 Jul 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene DNASE1L3 were set to Systemic lupus erythematosus, lupus nephritis, hypocomplementemic urticarial vasculitis, Diseases of Immune Dysregulation

26 Jun 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

DNASE1L3 was added to Primary immunodeficiency disorders panel. Sources: IUIS Classification February 2018

26 Jun 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

DNASE1L3 was created by Louise Daugherty