4-54288865-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006206.6(PDGFRA):​c.2741G>C​(p.Arg914Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

PDGFRA
NM_006206.6 missense

Scores

11
6
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.15
Variant links:
Genes affected
PDGFRA (HGNC:8803): (platelet derived growth factor receptor alpha) This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDGFRANM_006206.6 linkc.2741G>C p.Arg914Pro missense_variant Exon 20 of 23 ENST00000257290.10 NP_006197.1 P16234-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDGFRAENST00000257290.10 linkc.2741G>C p.Arg914Pro missense_variant Exon 20 of 23 1 NM_006206.6 ENSP00000257290.5 P16234-1
ENSG00000282278ENST00000507166.5 linkc.2021G>C p.Arg674Pro missense_variant Exon 21 of 24 2 ENSP00000423325.1 A0A0B4J203

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.67
.;D
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Uncertain
0.58
D
MutationAssessor
Benign
1.5
.;L
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-5.8
D;D
REVEL
Pathogenic
0.84
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.93
MutPred
0.78
.;Loss of MoRF binding (P = 0.0064);
MVP
0.96
MPC
3.4
ClinPred
1.0
D
GERP RS
6.1
Varity_R
0.94
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-55155032; API