NM_198253.3(TERT):c.2255A>G (p.His752Arg) AND Dyskeratosis congenita

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 15, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV002255341.10

Allele description [Variation Report for NM_198253.3(TERT):c.2255A>G (p.His752Arg)]

NM_198253.3(TERT):c.2255A>G (p.His752Arg)

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.2255A>G (p.His752Arg)

HGVS:

NC_000005.10:g.1278672T>C
NG_009265.1:g.21376A>G
NM_001193376.3:c.2255A>G
NM_198253.3:c.2255A>GMANE SELECT
NP_001180305.1:p.His752Arg
NP_937983.2:p.His752Arg
NP_937983.2:p.His752Arg
LRG_343t1:c.2255A>G
LRG_343:g.21376A>G
LRG_343p1:p.His752Arg
NC_000005.9:g.1278787T>C
NM_198253.2:c.2255A>G
NR_149162.3:n.2334A>G
NR_149163.3:n.2298A>G

Protein change:

H752R

Links:

dbSNP: rs375699185

NCBI 1000 Genomes Browser:

rs375699185

Molecular consequence:

NM_001193376.3:c.2255A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198253.3:c.2255A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_149162.3:n.2334A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_149163.3:n.2298A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Dyskeratosis congenita
Identifiers:: MONDO: MONDO:0015780; MedGen: C0265965; OMIM: PS127550

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002533128	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Sep 15, 2021)	germline	curation	Citation Link,
SCV002735252	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Feb 23, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002533128

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Sep 15, 2021)

germline

curation

Citation Link,

SCV002735252

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Feb 23, 2018)

germline

clinical testing

Citation Link

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, curation

Details of each submission

From Sema4, Sema4, SCV002533128.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

#	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

From Ambry Genetics, SCV002735252.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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

ClinVar

Relating variation to medicine