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NM_001099274.3(TINF2):c.844C>T (p.Arg282Cys) AND Dyskeratosis congenita, autosomal dominant 3

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Sep 1, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000005981.6

Allele description [Variation Report for NM_001099274.3(TINF2):c.844C>T (p.Arg282Cys)]

NM_001099274.3(TINF2):c.844C>T (p.Arg282Cys)

Gene:
TINF2:TERF1 interacting nuclear factor 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q12
Genomic location:
Preferred name:
NM_001099274.3(TINF2):c.844C>T (p.Arg282Cys)
HGVS:
  • NC_000014.9:g.24240636G>A
  • NG_016650.1:g.7039C>T
  • NG_054634.1:g.13220G>A
  • NM_001099274.3:c.844C>TMANE SELECT
  • NM_001363668.2:c.739C>T
  • NM_012461.3:c.844C>T
  • NP_001092744.1:p.Arg282Cys
  • NP_001350597.1:p.Arg247Cys
  • NP_036593.2:p.Arg282Cys
  • LRG_342t1:c.844C>T
  • LRG_342t2:c.844C>T
  • LRG_342:g.7039C>T
  • LRG_342p1:p.Arg282Cys
  • LRG_342p2:p.Arg282Cys
  • NC_000014.8:g.24709842G>A
  • NM_001099274.1:c.844C>T
Protein change:
R247C; ARG282CYS
Links:
OMIM: 604319.0004; dbSNP: rs121918545
NCBI 1000 Genomes Browser:
rs121918545
Molecular consequence:
  • NM_001099274.3:c.844C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363668.2:c.739C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012461.3:c.844C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Dyskeratosis congenita, autosomal dominant 3
Identifiers:
MONDO: MONDO:0013522; MedGen: C3151445; OMIM: 613990

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000026163OMIM
no assertion criteria provided
Pathogenic
(Nov 1, 2008) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV0025732733billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Sep 1, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes.

Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I.

Blood. 2008 Nov 1;112(9):3594-600. doi: 10.1182/blood-2008-05-153445. Epub 2008 Jul 30.

PubMed [citation]
PMID:
18669893
PMCID:
PMC2572788

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From OMIM, SCV000026163.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 7 patients with autosomal dominant dyskeratosis congenita-3 (DKCA3; 613990), Walne et al. (2008) identified a heterozygous 844C-T transition in exon 6 of the TINF2 gene, resulting in an arg282-to-cys (R282C) substitution.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From 3billion, SCV002573273.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. It is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88; 3Cnet: 0.70). Same nucleotide change resulting in same amino acid change (ClinVar ID: VCV000005627 ) and different missense changes at the same codon (p.Arg282His, p.Arg282Ser / ClinVar ID: VCV000005625 , VCV000005626 ) have been previously reported as pathogenic/likely pathogenic with strong evidence. Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024