NM_198253.3(TERT):c.2332G>A (p.Ala778Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 26, 2021
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:: RCV002563745.9

Allele description [Variation Report for NM_198253.3(TERT):c.2332G>A (p.Ala778Thr)]

NM_198253.3(TERT):c.2332G>A (p.Ala778Thr)

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.2332G>A (p.Ala778Thr)

HGVS:

NC_000005.10:g.1272235C>T
NG_009265.1:g.27813G>A
NM_001193376.3:c.2332G>A
NM_198253.3:c.2332G>AMANE SELECT
NP_001180305.1:p.Ala778Thr
NP_937983.2:p.Ala778Thr
LRG_343t1:c.2332G>A
LRG_343:g.27813G>A
NC_000005.9:g.1272350C>T
NM_198253.2:c.2332G>A

Protein change:

A778T

Links:

dbSNP: rs781360741

NCBI 1000 Genomes Browser:

rs781360741

Molecular consequence:

NM_001193376.3:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198253.3:c.2332G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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RecName: Full=Zinc finger protein 10; AltName: Full=Zinc finger protein KOX1
RecName: Full=Zinc finger protein 10; AltName: Full=Zinc finger protein KOX1
gi|55977778|sp|P21506.3|ZNF10_HUMAN

Protein
RecName: Full=Deleted in azoospermia-like; AltName: Full=DAZ homolog; AltName: F...
RecName: Full=Deleted in azoospermia-like; AltName: Full=DAZ homolog; AltName: Full=DAZ-like autosomal; AltName: Full=Deleted in azoospermia-like 1; AltName: Full=SPGY-like-autosomal
gi|27805453|sp|Q92904.1|DAZL_HUMAN

Protein
ZP2 zona pellucida glycoprotein 2 [Homo sapiens]
ZP2 zona pellucida glycoprotein 2 [Homo sapiens]
Gene ID:7783

Gene
7783[uid] AND (alive[prop]) (1)
Gene
hscC chaperone protein HscC [Escherichia coli str. K-12 substr. MG1655]
hscC chaperone protein HscC [Escherichia coli str. K-12 substr. MG1655]
Gene ID:945218

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001403213	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 26, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001403213

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 26, 2021)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001403213.4

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

Description

This sequence change replaces alanine with threonine at codon 778 of the TERT protein (p.Ala778Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TERT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Oct 26, 2024

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