chr4:55152093:A>T Detail (hg19) (PDGFRA)

Information

Genome

Assembly Position
hg19 chr4:55,152,093-55,152,093
hg38 chr4:54,285,926-54,285,926 View the variant detail on this assembly version.

HGVS

Type Transcript Protein
RefSeq NM_006206.4:c.2525A>T NP_006197.1:p.Asp842Val
Ensemble ENST00000257290.10:c.2525A>T ENST00000257290.10:p.Asp842Val
Summary

MGeND

Clinical significance
Variant entry
GWAS entry
Disease area statistics Show details

Frequency

[No Data.]

Prediction

ClinVar

Clinical Significance Conflicting classifications of pathogenicity
Review star
Show details
Links
Type Database ID Link
Gene MIM 173490 OMIM
HGNC 8803 HGNC
Ensembl ENSG00000134853 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC COSM736 COSMIC
MONDO
Disease area statistics
[No Data.]
MGeND
[No Data.]
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Pathogenic 2016-03-10 no assertion criteria provided gastrointestinal stromal tumor somatic Detail
Uncertain significance no assertion criteria provided not provided unknown Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
gastrointestinal stromal tumor Imatinib B Predictive Supports Resistance Somatic 4 15928335 Detail
gastrointestinal stromal tumor Imatinib B Predictive Supports Resistance Somatic 4 16954519 Detail
gastrointestinal stromal tumor B Diagnostic Supports Negative Somatic 3 15146165 Detail
cancer Imatinib D Predictive Supports Resistance Somatic 2 14645423 Detail
gastrointestinal stromal tumor Imatinib C Predictive Supports Resistance Somatic 2 14645423 Detail
cancer Sunitinib D Predictive Supports Resistance Somatic 2 18955458 Detail
gastrointestinal stromal tumor Crenolanib D Predictive Supports Sensitivity/Response Somatic 4 22745105 Detail
gastrointestinal stromal tumor Sunitinib C Predictive Supports Resistance Somatic 3 18955458 Detail
cancer Imatinib Mesylate D Predictive Supports Resistance Somatic 2 18955458 Detail
gastrointestinal stromal tumor Imatinib D Predictive Supports Resistance Somatic 3 12949711 Detail
gastrointestinal stromal tumor Imatinib B Predictive Supports Resistance Somatic 4 26130666 Detail
DisGeNET
Score Disease name Description Source Pubmed Links
<0.001 Fibroid Tumor Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) ha... BeFree 24618081 Detail
0.616 Gastrointestinal Stromal Tumors NA CLINVAR Detail
0.001 Gastrointestinal Stromal Tumors We performed an association study between copy number alterations (CNAs) identif... BeFree 24124608 Detail
0.616 Gastrointestinal Stromal Tumors The choice also should be personalized on the basis of genotype: generally, PDGF... BeFree 22743760 Detail
0.760 Gastrointestinal Stromal Tumors Previously, we found 2 types of gain-of-function mutation of the PDGFRA gene, Va... BeFree 15221957 Detail
0.616 Gastrointestinal Stromal Tumors Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with ima... BeFree 22745105 Detail
0.001 Fibroid Tumor Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) ha... BeFree 24618081 Detail
0.616 Gastrointestinal Stromal Tumors PDGFRA exon 18 mutations (total 86 cases) were common in epithelioid GISTs and m... BeFree 15613856 Detail
0.002 Gastrointestinal Stromal Tumors mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.04... BeFree 24124608 Detail
0.003 Hypereosinophilia Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) ha... BeFree 24618081 Detail
0.250 Gastrointestinal Stromal Tumors mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.04... BeFree 24124608 Detail
0.616 Gastrointestinal Stromal Tumors Previously, we found 2 types of gain-of-function mutation of the PDGFRA gene, Va... BeFree 15221957 Detail
0.002 Gastrointestinal Stromal Tumors mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.04... BeFree 24124608 Detail
0.005 Gastrointestinal Stromal Tumors mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.04... BeFree 24124608 Detail
0.003 Gastrointestinal Stromal Tumors mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.04... BeFree 24124608 Detail
<0.001 polyps Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) ha... BeFree 24618081 Detail
<0.001 Gastrointestinal Stromal Tumors Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) ha... BeFree 24618081 Detail
<0.001 polyps Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) ha... BeFree 24618081 Detail
0.616 Gastrointestinal Stromal Tumors Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) ha... BeFree 24618081 Detail
0.616 Gastrointestinal Stromal Tumors qRT-PCR validation of the GSTT1 results in this cohort and 11 additional maligna... BeFree 24124608 Detail
Annotation

Annotations

DescrptionSourceLinks
GIST cancer with D842V mutation is resistant to imatinib. CIViC Evidence Detail
While cancer with PDGFRA V561D mutation is known to be sensitive to Imatinib, double mutation of V56... CIViC Evidence Detail
GIST tumors harboring PDGFRA D842V mutation are more likely to be benign than malignant. CIViC Evidence Detail
In an in vitro study of imatinib sensitivity, PDGFRA D842V was cloned into a plasmid by site-directe... CIViC Evidence Detail
This prospective study of 127 patients with metastatic gastrointestinal stromal tumors (GISTs) exami... CIViC Evidence Detail
In an in vitro study, Chinese hamster ovary cells expressing PDGFRA D842V mutation demonstrated redu... CIViC Evidence Detail
In CHO cells with PDGFRA D842V mutation that have shown imatinib resistance, crenolanib was signific... CIViC Evidence Detail
Patients 29 and 66 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or int... CIViC Evidence Detail
In an in vitro study, Chinese hamster ovary cells expressing PDGFRA D842V mutation demonstrated redu... CIViC Evidence Detail
When 293T cells stably transduced with PDGFRA A842V were treated with imatinib, tyrosine phosphoryla... CIViC Evidence Detail
823 patients with GIST under therapy with imatinib were genotyped for this study. 18 patients (2%) w... CIViC Evidence Detail
NM_006206.6(PDGFRA):c.2525A>T (p.Asp842Val) AND Gastrointestinal stromal tumor ClinVar Detail
NM_006206.6(PDGFRA):c.2525A>T (p.Asp842Val) AND not provided ClinVar Detail
Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in... DisGeNET Detail
NA DisGeNET Detail
We performed an association study between copy number alterations (CNAs) identified from array CGH a... DisGeNET Detail
The choice also should be personalized on the basis of genotype: generally, PDGFRA D842V mutated and... DisGeNET Detail
Previously, we found 2 types of gain-of-function mutation of the PDGFRA gene, Val561 to Asp and Asp8... DisGeNET Detail
Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gast... DisGeNET Detail
Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in... DisGeNET Detail
PDGFRA exon 18 mutations (total 86 cases) were common in epithelioid GISTs and most commonly represe... DisGeNET Detail
mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.041), whereas mRNA exp... DisGeNET Detail
Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in... DisGeNET Detail
mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.041), whereas mRNA exp... DisGeNET Detail
Previously, we found 2 types of gain-of-function mutation of the PDGFRA gene, Val561 to Asp and Asp8... DisGeNET Detail
mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.041), whereas mRNA exp... DisGeNET Detail
mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.041), whereas mRNA exp... DisGeNET Detail
mRNA expression levels of all SDH gene subunits were significantly lower (P≤0.041), whereas mRNA exp... DisGeNET Detail
Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in... DisGeNET Detail
Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in... DisGeNET Detail
Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in... DisGeNET Detail
Activated forms of the platelet derived growth factor receptor alpha (PDGFRα) have been described in... DisGeNET Detail
qRT-PCR validation of the GSTT1 results in this cohort and 11 additional malignant GISTs showed a si... DisGeNET Detail

Overlapped Transcript Coordinates

Gene Transcript ID Exon Number Chromosome Start Stop Type Amino Mutation Transcript Position Links

Overlapped Transcript

Gene Transcript ID Chromosome Start Stop Links
Gene
-
dbSNP
rs121908585 dbSNP
Genome
hg19
Position
chr4:55,152,093-55,152,093
Variant Type
snv
Reference Allele
A
Alternative Allele
T
Variant (CIViC) (CIViC Variant)
D842V
Transcript 1 (CIViC Variant)
ENST00000257290.5
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/99
Summary (CIViC Variant)
PDGFRA D842 mutations are characterized broadly as imatinib resistance mutations. This is most well characterized in gastrointestinal stromal tumors, but other cell lines containing these mutations have been shown to be resistant as well. Exogenous expression of the A842V mutation resulted in constitutive tyrosine phosphorylation of PDGFRA in the absence of ligand in 293T cells and cytokine-independent proliferation of the IL-3-dependent Ba/F3 cell line, both evidence that this is an activating mutation. In imatinib resistant cell lines, a number of other therapeutics have demonstrated efficacy. These include; crenolanib, sirolimus, and midostaurin (PKC412).
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