COVID-19 researchGene: TINF2
Immunodeficiency not a predominant manifestation
Created: 29 Jun 2018, 3:34 p.m.
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.
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.
Source Expert Review Green was added to TINF2. Added phenotypes microcephaly, neurodevelopmental delay exudative retinopathy; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay for gene: TINF2 Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: TINF2 was added gene: TINF2 was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification February 2018,Expert Review Amber Mode of inheritance for gene: TINF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TINF2 were set to 18252230; 21199492; 21477109; 18979121; 27033759; 18669893; 29742735 Phenotypes for gene: TINF2 were set to microcephaly, neurodevelopmental delay exudative retinopathy; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay