NM_198253.3(TERT):c.887A>C (p.His296Pro) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Oct 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000471556.6

Allele description [Variation Report for NM_198253.3(TERT):c.887A>C (p.His296Pro)]

NM_198253.3(TERT):c.887A>C (p.His296Pro)

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.887A>C (p.His296Pro)
HGVS:
  • NC_000005.10:g.1293999T>G
  • NG_009265.1:g.6049A>C
  • NM_001193376.3:c.887A>C
  • NM_198253.2:c.887A>C
  • NM_198253.3:c.887A>CMANE SELECT
  • NP_001180305.1:p.His296Pro
  • NP_937983.2:p.His296Pro
  • NP_937983.2:p.His296Pro
  • LRG_343t1:c.887A>C
  • LRG_343:g.6049A>C
  • LRG_343p1:p.His296Pro
  • NC_000005.9:g.1294114T>G
  • NM_001193376.1:c.887A>C
  • NR_149162.3:n.966A>C
  • NR_149163.3:n.966A>C
Protein change:
H296P
Links:
dbSNP: rs778187343
NCBI 1000 Genomes Browser:
rs778187343
Molecular consequence:
  • NM_001193376.3:c.887A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198253.2:c.887A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198253.3:c.887A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149162.3:n.966A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_149163.3:n.966A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Idiopathic Pulmonary Fibrosis (ILD2)
Synonyms:
Fibrosing alveolitis, cryptogenic; Familial idiopathic pulmonary fibrosis; Fibrocystic pulmonary dysplasia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008345; MedGen: C1800706; Orphanet: 2032; Orphanet: 79126; OMIM: 178500
Name:
Dyskeratosis congenita, autosomal dominant, 2 (DKCA2)
Identifiers:
MONDO: MONDO:0013521; MedGen: C3151443; OMIM: 613989

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000551510Invitaecriteria provided, single submitter
Uncertain significance
(Oct 30, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease.

Donati B, Pietrelli A, Pingitore P, Dongiovanni P, Caddeo A, Walker L, Baselli G, Pelusi S, Rosso C, Vanni E, Daly A, Mancina RM, Grieco A, Miele L, Grimaudo S, Craxi A, Petta S, De Luca L, Maier S, Soardo G, Bugianesi E, Colli F, et al.

Cancer Med. 2017 Aug;6(8):1930-1940. doi: 10.1002/cam4.1078. Epub 2017 Jul 4.

PubMed [citation]
PMID:
28677271
PMCID:
PMC5548883

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000551510.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces histidine with proline at codon 296 of the TERT protein (p.His296Pro). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and proline. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an individual affected with primary liver cancer (PMID: 28677271). ClinVar contains an entry for this variant (Variation ID: 268080). 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 addition, an experimental study has shown that recombinant proteins containing this variant were expressed at similar levels as the wild-type TERT protein in cultured human cell lines (PMID: 28677271). However, the clinical significance of these results is uncertain. 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.

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

Last Updated: Nov 20, 2021

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