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Primary immunodeficiency

Gene: NHP2

Green List (high evidence)

NHP2 (NHP2 ribonucleoprotein)
EnsemblGeneIds (GRCh38): ENSG00000145912
EnsemblGeneIds (GRCh37): ENSG00000145912
OMIM: 606470, Gene2Phenotype
NHP2 is in 15 panels

5 reviews

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)

Sarah Leigh (Genomics England Curator)

Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 3 variants reported in 2 cases. The patients had shortened telomeres and decreased levels of serum TERC (602322) RNA. Functional expression studies in HeLa cells showed that TERC levels were increased when wildtype NHP2 was expressed in cells containing the variant (c.415T>C) NHP2 (PMID 18523010).
Created: 2 May 2018, 2:15 p.m.

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
Comment on list classification: Changed Amber to Green from external review comment and further publications to support gene-disease association
Created: 4 Jul 2018, 4:21 p.m.
Comment on publications: Added publications to support upgrading of the gene to Green. Biallelic variants of the gene NHP2 are known to cause Dyskeratosis congenital (DC) and have been reported in three families to date PMID: 18523010, . From Savage et al, 2009 PMID:20301779 patients with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Loss-of-function variants in NHP2 are known to be pathogenic (PMID: 18523010, 20008900). For these reasons, this variant has been classified as Pathogenic.
Created: 4 Jul 2018, 4:15 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): NHP2 .PanelApp HGNC gene symbol check: NHP2 . IUIS Disease: AR-DKC due to nucleolar protein family A member 2 (NHP2) 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.
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: NHP2, PanelApp HGNC gene symbol check: NHP2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Dyskeratosis congenita / Dyskeratosis congenita; 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: NHP2, GRID_Gene_Symbol: NHP2, GRID_Transcript_ENS_Community submitted: ENST00000274606, GRID_Transcript_RefSeq: NM_017838.3, GRID_Transcript_ENS_used_on_Production: ENST00000274606
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
  • Expert Review Green
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Dyskeratosis congenita, autosomal recessive 2 613987
  • Dyskeratosis congenita
  • 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
OMIM
606470
Clinvar variants
Variants in NHP2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to NHP2.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to NHP2.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to NHP2.

12 Jul 2018, Gel status: 3

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.

4 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: nhp2 has been classified as Green List (High Evidence).

4 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: nhp2 has been classified as Green List (High Evidence).

4 Jul 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: NHP2 were set to 25182133; 18523010; 25907943; 20301779; 20008900

4 Jul 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: NHP2 were set to 25182133; 18523010; 25907943; 20301779

1 Jul 2018, Gel status: 2

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene NHP2 were set to Dyskeratosis congenita, autosomal recessive 2 613987, Dyskeratosis congenita, 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: 2

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to NHP2. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to NHP2. Panel: Primary immunodeficiency disorders

2 May 2018, Gel status: 2

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

2 May 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for NHP2 were set to 18523010

2 May 2018, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for NHP2 were set to Dyskeratosis congenita, autosomal recessive 2 613987; Dyskeratosis congenita; Hoyeraal-Hreidarsson syndrome

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to NHP2. 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 NHP2. Panel: Primary immunodeficiency disorders Phenotypes for gene NHP2 were set to Dyskeratosis congenita, 2, Dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene NHP2 were set to Dyskeratosis congenita, 2

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

NHP2 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

NHP2 was created by Louise Daugherty