Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: NHP2
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
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.
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 associationCreated: 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 TelomeresCreated: 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 syndromeCreated: 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: ENST00000274606Created: 17 Apr 2018, 12:12 p.m.
Source NHS GMS was added to NHP2.
Source North West GLH was added to NHP2.
Source London North GLH was added to NHP2.
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.
Gene: nhp2 has been classified as Green List (High Evidence).
Gene: nhp2 has been classified as Green List (High Evidence).
Publications for gene: NHP2 were set to 25182133; 18523010; 25907943; 20301779; 20008900
Publications for gene: NHP2 were set to 25182133; 18523010; 25907943; 20301779
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
IUIS Classification February 2018 was added to NHP2. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to NHP2. Panel: Primary immunodeficiency disorders
This gene has been classified as Amber List (Moderate Evidence).
Publications for NHP2 were set to 18523010
Phenotypes for NHP2 were set to Dyskeratosis congenita, autosomal recessive 2 613987; Dyskeratosis congenita; Hoyeraal-Hreidarsson syndrome
Expert Review Amber was added to NHP2. Panel: Primary immunodeficiency disorders
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
Phenotypes for gene NHP2 were set to Dyskeratosis congenita, 2
NHP2 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
NHP2 was created by Louise Daugherty