NM_198253.3(TERT):c.2431C>T (p.Arg811Cys) AND Dyskeratosis congenita, autosomal dominant 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 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:: RCV002051796.8

Allele description [Variation Report for NM_198253.3(TERT):c.2431C>T (p.Arg811Cys)]

NM_198253.3(TERT):c.2431C>T (p.Arg811Cys)

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.2431C>T (p.Arg811Cys)

HGVS:

NC_000005.10:g.1271156G>A
NG_009265.1:g.28892C>T
NM_001193376.3:c.2431C>T
NM_198253.3:c.2431C>TMANE SELECT
NP_001180305.1:p.Arg811Cys
NP_937983.2:p.Arg811Cys
NP_937983.2:p.Arg811Cys
LRG_343t1:c.2431C>T
LRG_343:g.28892C>T
LRG_343p1:p.Arg811Cys
NC_000005.9:g.1271271G>A
NM_198253.2:c.2431C>T
O14746:p.Arg811Cys

Protein change:

R811C; ARG811CYS

Links:

UniProtKB: O14746#VAR_062540; OMIM: 187270.0012; dbSNP: rs199422301

NCBI 1000 Genomes Browser:

rs199422301

Molecular consequence:

NM_001193376.3:c.2431C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198253.3:c.2431C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002318673	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28192371, 17785587, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002318673

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 22, 2022)

germline

clinical testing

PubMed (3)
[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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations.

Maryoung L, Yue Y, Young A, Newton CA, Barba C, van Oers NS, Wang RC, Garcia CK.

J Clin Invest. 2017 Mar 1;127(3):982-986. doi: 10.1172/JCI91161. Epub 2017 Feb 13.

PubMed [citation]

PMID:: 28192371
PMCID:: PMC5330735

Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome.

Marrone A, Walne A, Tamary H, Masunari Y, Kirwan M, Beswick R, Vulliamy T, Dokal I.

Blood. 2007 Dec 15;110(13):4198-205. Epub 2007 Sep 4.

PubMed [citation]

PMID:: 17785587
PMCID:: PMC2882230

See all PubMed Citations (3)

Details of each submission

From 3billion, SCV002318673.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004). A missense variant is a common mechanism. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Nov 24, 2024

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