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Primary immunodeficiency

Gene: TINF2

Amber List (moderate evidence)

TINF2 (TERF1 interacting nuclear factor 2)
EnsemblGeneIds (GRCh38): ENSG00000092330
EnsemblGeneIds (GRCh37): ENSG00000092330
OMIM: 604319, Gene2Phenotype
TINF2 is in 21 panels

3 reviews

Sophie Hambleton (Newcastle University)

I don't know

Immunodeficiency not a predominant manifestation
Created: 29 Jun 2018, 3:34 p.m.

Eleanor Williams (Genomics England Curator)

Comment on publications: Adding publications listing variants
Created: 19 Jun 2018, 1:01 p.m.
Keeping gene as amber because, as with TERT and TERC, lack of PID phenotype in most individuals.
Created: 19 Jun 2018, 12:59 p.m.
In OMIM TINF2 is associated with Dyskeratosis congenita, autosomal dominant 3. OMIM report that Savage et al. (2008) (PMID: 18252230) reported 4 members of a family with autosomal dominant dyskeratosis congenita-3 with a K280E substitution. The mutation was also found in 2 family members who were classified as silent carriers because, while they showed some clinical features, did not meet the clinical definition of DKC. A R282H substitution was identified in 3 patients by Savage et al. (2008) (PMID: 18252230). Two of these patients had the 'DKC triad', one additionally with Revesz syndrome. The third patient without the DKC triad had dystrophic nails and IgA deficiency. The R282H substitution was also identified as a de novo heterozygous mutation in an 18-month girl with DKC by Tsangaris et al. (2008)(PMID:18979121) and Vulliamy et al. (2012) (PMID: 21199492) identified the heterozygous R282H mutation in 7 unrelated patients with DKC. Walne et al. (2008) (PMID: Nonsense and frameshift mutations have been reported by Sasa et al. (2012)(PMID: 21477109) and Vulliamy et al. (2012). More recently Wan et al (2016) (PMID: 27033759) report TINF2 mutations in several patients with dyskeratosis congenital with bone marrow failure, some in combination with variants in TERT and DKC1. Du et al (2018) (PMID: 29742735) report a patient with DKC and pulmonary fibrosis and an Arg282Cys change in TINF2.
Created: 19 Jun 2018, 12:54 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): TINF2. PanelApp HGNC gene symbol check: TINF2 . IUIS Disease: AD-DKC due to TINF2 deficiency . IUIS Inheritance: AD .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. IUIS Major category: Bone marrow failure IUIS Subcategory: none given
Created: 28 Feb 2020, 5:03 p.m. | Last Modified: 28 Feb 2020, 5:03 p.m.
Panel Version: 2.28
Keep Amber until more info on gene and disease association, expert review agrees that Immunodeficiency not a predominant manifestation. Request evidences from GRID and Victorian Clinical Genetics Services.
Created: 5 Jul 2018, 1:44 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TINF2 .PanelApp HGNC gene symbol check: TINF2 . IUIS Disease: AD-DKC due to TINF2 deficiency . IUIS Inheritance: AD .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: 19 Apr 2018, 12:43 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: TINF2, PanelApp HGNC gene symbol check: TINF2, 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: TINF2, GRID_Gene_Symbol: TINF2, GRID_Transcript_ENS_Community submitted: ENST00000267415, GRID_Transcript_RefSeq: NM_012461.2, GRID_Transcript_ENS_used_on_Production: ENST00000267415
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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 exudative retinopathy
OMIM
604319
Clinvar variants
Variants in TINF2
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: TINF2 were changed from DBone 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 exudative retinopathy 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 exudative retinopathy

28 Feb 2020, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TINF2 were changed from Dyskeratosis congenita 3; 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 DBone 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 exudative retinopathy

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: tinf2 has been classified as Amber List (Moderate Evidence).

1 Jul 2018, Gel status: 2

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TINF2 were set to Dyskeratosis congenita 3, 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 TINF2. 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 TINF2. Panel: Primary immunodeficiency disorders

19 Jun 2018, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TINF2 were set to 18252230; 18979121; 21199492; 21477109; 29742735; 27033759; 18669893

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 TINF2. Panel: Primary immunodeficiency disorders Phenotypes for gene TINF2 were set to Dyskeratosis congenita 3, Dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TINF2 were set to Dyskeratosis congenita 3

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

TINF2 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

TINF2 was created by Louise Daugherty