ETV6
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ETV6 (HGNC:3495) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
ETS variant transcription factor 6
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
TEL
%HI
1.55(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.44(Read more about gnomAD LOEUF score)
Cytoband
12p13.2
Genomic Coordinates
GRCh37/hg19: chr12:11802608-12048311 NCBI Ensembl UCSC
GRCh38/hg38: chr12:11649674-11895377 NCBI Ensembl UCSC
MANE Select Transcript
NM_001987.5 ENST00000396373.9 (Read more about MANE Select)
Function
Transcriptional repressor; binds to the DNA sequence 5'- CCGGAAGT-3'. Plays a role in hematopoiesis and malignant transformation. {ECO:0000269|PubMed:25581430}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-27620
ClinGen Curation ID:
CCID:007091
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Assoc. with Reduced Penetrance:
Yes
The penetrance of thrombocytopenia in this disorder is thought to exceed 90%. The penetrance of malignancy, specifically lymphoid and myeloid, is estimated at 30%.
Last Evaluated:
01/11/2023

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Thrombocytopenia 5 OMIM
HI Evidence:
  • PUBMED: 26522332
    Moriyama 2015. WES identified a novel non-sense ETV6 variant (p.Arg359X) with a high penetrance in an index family with 3 members of ALL (mother and 2 daughter, at the ages of 9, 3, and 2). 1 daughter with the same (11 yro then) did not have leukemia at the time when this manuscript was written, suggesting possible incomplete penetrance. Subsequent targeted sequencing of ETV6 in 4405 childhood ALL cases identified 31 exonic variants (four non-sense, 21 missense, one splice site, and five frameshift variants) that were potentially related to ALL risk in 35 cases (1%).
  • PUBMED: 30940639
    Rampersaud 2019. WGS identified a germline 75-bp deletion, removing ETV6 exon 7 splice acceptor, resulting in exon skipping and protein truncation, in 4 of 7 affected individuals from a kindred presenting with pre–B-cell ALL, diffuse large B-cell lymphoma (DLBCL), thrombocytopenia, and aplastic anemia.
  • PUBMED: 26102509
    Topka 2015. Sanger sequencing ETV6 p. N385fs (c.1153-5_1153_1delAACAG) was identified in 2 affected members from a kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. FUNCTIONAL study showed leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes.
  • PUBMED: 27365488
    Melazzini 2016. ETV6 gene was analyzed using Sanger and whole exome sequencing in the 130 families with inherited thrombocytopenia of unknown origin. identified 5 ETV6 variants in 20 patients with ETV6-related thrombocytopenia from 7 pedigrees. One family (3 affected members) has a fs variant (c.1153-1_1165del/p.N385Vfs*7) which resulting in skipping of e7 and truncation of the ETS domain.
  • PUBMED: 25807284
    Noetzli 2015. WES identified a splicing variant (c.1252A>G) in ETV6 segregating in 2 affected members from a family with thrombocytopenia and elevated MCV. This variant leads to skipping of exon 7 and a subsequent p.Asn385Valfs*7, affecting the putative DNA binding domain.
  • PUBMED: 28104920
    Guidugli 2017. NGS MDS/AL predisposition gene panel analysis in 197 patients identified a novel c.614del /p.Leu205Argfs4 in ETV6 gene in a patient with MDS/acute leukemia
HI Evidence Comments:
Haploinsufficiency of this ETV6 cause autosomal dominant ETV6 thrombocytopenia and predisposition to leukemia. Three more nonsense variants were reported by PMID: 32935436 and PMID: 31704777.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000012.11) (NC_000012.12)