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Primary immunodeficiency

Gene: TERT

Amber List (moderate evidence)

TERT (telomerase reverse transcriptase)
EnsemblGeneIds (GRCh38): ENSG00000164362
EnsemblGeneIds (GRCh37): ENSG00000164362
OMIM: 187270, Gene2Phenotype
TERT is in 26 panels

3 reviews

Sophie Hambleton (Newcastle University)

I don't know

Clinical correlation will be required (this is the case for many genes in this panel!!)
Created: 29 Jun 2018, 3:32 p.m.

Eleanor Williams (Genomics England Curator)

Comment on list classification: Keeping gene as amber after review from Genomics England clinical team. Lack of PID phenotype in the majority of individuals.
Created: 19 Jun 2018, 9:30 a.m.
Asked for Genomics England clinical team input as to whether this gene should be rated green, even though there are enough cases, since there is incomplete penetrance and variable clinical phenotypes relating to immunodeficiency.
Created: 14 Jun 2018, 12:44 p.m.
Comment on phenotypes: Added Phenotype MIM numbers.
Created: 14 Jun 2018, 12:36 p.m.
Comment on publications: Added publications relating to reported variants
Created: 14 Jun 2018, 12:35 p.m.
Comment on mode of inheritance: {Dyskeratosis congenita, autosomal dominant 2} inheritance appears to be monoallelic, {Dyskeratosis congenita, autosomal recessive 4} inheritance appears to be biallelic. Confirmed by OMIM entry. Note also anticipation may be seen.
Created: 14 Jun 2018, 12:34 p.m.
Added missense tag as all variants to date are missense.
Created: 14 Jun 2018, 12:31 p.m.
OMIM reports that TERT is associated with {Dyskeratosis congenita, autosomal dominant 2} and {Dyskeratosis congenita, autosomal recessive 4}. Armanios et al. (2005) (PMID: 16247010) report a heterozygous mutation (K902N substitution in a highly conserved residue) in the TERT gene in 6 members of a family with autosomal dominant dyskeratosis congenita-2. In vitro functional expression studies showed that the K902N mutant protein had almost no telomerase activity, resulting in haploinsufficiency. Anticipation of clinical features was observed. Basel-Vanagaite et al. (2008) (PMID: 18460650]) identified a heterozygous mutation in the TERT gene (R631Q, conserved residue in motif 2 of the RT domain) in affected members of an Iraqi Jewish family with autosomal dominant dyskeratosis congenita-2. Marrone et al. (2007) (PMID: 17785587) reported two variants in unrelated patients with autosomal recessive dyskeratosis congenita-4; R811C is in nonconserved region of the RT domain, R901W is in a conserved region of the RT domain. Du et al. (2008) (PMID: 18042801) report another case of autosomal recessive dyskeratosis congenita-4 with the individual having a P704S variant. In a PubMed search a report by Vulliamy et al 2005 (PMID: 15885610) was found which reports on several TERT variants including two non-sense mutations R979W and F1127L that may have functional consequences in patients with dyskeratosis congenita/aplastic anemia, however only mutations in the TERT gene were looked for in these patients. More than 3 cases of plausible disease causing mutations. All missense. Note anticipation may be a feature of this gene-disease association.
Created: 14 Jun 2018, 12:29 p.m.

Louise Daugherty (Genomics England Curator)

I don't know

OriginaI Metadata from IUIS classification table (December, 2019). IUIS Genetic defect (original gene symbol in IUIS download): TERT .PanelApp HGNC gene symbol check: TERT . IUIS Disease: AD/AR-DKC due to TERT deficiency . IUIS Inheritance: AD or AR .T cells: normal to low / normal to low, .B cells: Normal to low / normal to low, .IUIS Other affected cells: Hematopoietic stem cell / Hematopoietic stem cell. IUIS Associated features: Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay / Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay. IUIS Major category: Bone marrow failure, UIS Subcategory: none given
Created: 28 Feb 2020, 5 p.m. | Last Modified: 28 Feb 2020, 5 p.m.
Panel Version: 2.28
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TERT .PanelApp HGNC gene symbol check: TERT . IUIS Disease: AD/AR-DKC due to TERT deficiency . IUIS Inheritance: AD or AR .T cells: Variable, .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: 19 Apr 2018, 1:08 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: TERT, PanelApp HGNC gene symbol check: TERT, 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: TERT, GRID_Gene_Symbol: TERT, GRID_Transcript_ENS_Community submitted: ENST00000310581, GRID_Transcript_RefSeq: NM_198253.2, GRID_Transcript_ENS_used_on_Production: ENST00000310581
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation
  • microcephaly, neurodevelopmental delay
  • Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation
  • microcephaly, neurodevelopmental delay
  • Bone marrow failure
Tags
missense
OMIM
187270
Clinvar variants
Variants in TERT
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Feb 2020, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TERT were changed from Dyskeratosis congenita 2 613989, Dyskeratosis congenita 4 613989; 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 to Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay; Bone marrow failure

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.

5 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

1 Jul 2018, Gel status: 2

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TERT were set to Dyskeratosis congenita 2 613989, Dyskeratosis congenita 4 613989, 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 TERT. 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 TERT. Panel: Primary immunodeficiency disorders

19 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

14 Jun 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TERT were set to Dyskeratosis congenita 2 613989, Dyskeratosis congenita 4 613989; Dyskeratosis congenita; Hoyeraal-Hreidarsson syndrome

14 Jun 2018, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TERT were set to 16247010; 18460650; 15885610; 17785587

14 Jun 2018, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: TERT was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 Apr 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to TERT. Panel: Primary immunodeficiency disorders Phenotypes for gene TERT were set to Dyskeratosis congenita 2, Dyskeratosis congenita 4, Dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TERT were set to Dyskeratosis congenita 2, Dyskeratosis congenita 4

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

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

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

TERT was created by Louise Daugherty