NM_198253.3(TERT):c.2320C>T (p.Arg774Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2023
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:: RCV002525003.10

Allele description [Variation Report for NM_198253.3(TERT):c.2320C>T (p.Arg774Ter)]

NM_198253.3(TERT):c.2320C>T (p.Arg774Ter)

Gene:

TERT:telomerase reverse transcriptase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p15.33

Genomic location:

Preferred name:

NM_198253.3(TERT):c.2320C>T (p.Arg774Ter)

HGVS:

NC_000005.10:g.1272247G>A
NG_009265.1:g.27801C>T
NM_001193376.3:c.2320C>T
NM_198253.3:c.2320C>TMANE SELECT
NP_001180305.1:p.Arg774Ter
NP_937983.2:p.Arg774Ter
NP_937983.2:p.Arg774Ter
LRG_343t1:c.2320C>T
LRG_343:g.27801C>T
LRG_343p1:p.Arg774Ter
NC_000005.9:g.1272362G>A
NM_198253.2:c.2320C>T

Protein change:

R774*

Links:

dbSNP: rs770066110

NCBI 1000 Genomes Browser:

rs770066110

Molecular consequence:

NM_001193376.3:c.2320C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_198253.3:c.2320C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Dyskeratosis congenita, autosomal dominant 2
Identifiers:: MONDO: MONDO:0013521; MedGen: C3151443; OMIM: 613989

Name:: Idiopathic Pulmonary Fibrosis
Synonyms:: Idiopathic fibrosing alveolitis, chronic form
Identifiers:: MeSH: D054990; MedGen: C1800706

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Brassicaceae internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA...
Brassicaceae internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence.
PopSet: 90994927

PopSet
Homo sapiens mRNA for calcium-binding protein in amniotic fluid 1, complete cds
Homo sapiens mRNA for calcium-binding protein in amniotic fluid 1, complete cds
gi|1694618|dbj|D49549.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001230882	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29483670, 16247010, 17460043, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001230882

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 27, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel variants in Nordic patients referred for genetic testing of telomere-related disorders.

Norberg A, Rosén A, Raaschou-Jensen K, Kjeldsen L, Moilanen JS, Paulsson-Karlsson Y, Baliakas P, Lohi O, Ahmed A, Kittang AO, Larsson P, Roos G, Degerman S, Hultdin M.

Eur J Hum Genet. 2018 Jun;26(6):858-867. doi: 10.1038/s41431-018-0112-8. Epub 2018 Feb 26.

PubMed [citation]

PMID:: 29483670
PMCID:: PMC5974393

Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita.

Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW.

Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15960-4. Epub 2005 Oct 24.

PubMed [citation]

PMID:: 16247010
PMCID:: PMC1276104

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001230882.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 446373). This premature translational stop signal has been observed in individual(s) with clinical features consistent with TERT-related conditions (PMID: 29483670). This variant is present in population databases (rs770066110, gnomAD 0.06%). This sequence change creates a premature translational stop signal (p.Arg774*) in the TERT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TERT are known to be pathogenic (PMID: 16247010, 17460043).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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