4-54273597-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006206.6(PDGFRA):ā€‹c.1425G>Cā€‹(p.Glu475Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

PDGFRA
NM_006206.6 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.643
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10603267).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PDGFRANM_006206.6 linkc.1425G>C p.Glu475Asp missense_variant 10/23 ENST00000257290.10 NP_006197.1 P16234-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PDGFRAENST00000257290.10 linkc.1425G>C p.Glu475Asp missense_variant 10/231 NM_006206.6 ENSP00000257290.5 P16234-1
ENSG00000282278ENST00000507166.5 linkc.1018-1328G>C intron_variant 2 ENSP00000423325.1 A0A0B4J203
PDGFRAENST00000509092.5 linkn.1243G>C non_coding_transcript_exon_variant 9/151
PDGFRAENST00000509490.5 linkn.1425G>C non_coding_transcript_exon_variant 10/181 ENSP00000424218.1 P16234-3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461830
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
11
DANN
Benign
0.95
DEOGEN2
Benign
0.067
T
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
1.3
L
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.39
N
REVEL
Benign
0.12
Sift
Benign
0.30
T
Sift4G
Benign
0.38
T
Polyphen
0.0
B
Vest4
0.30
MutPred
0.19
Loss of sheet (P = 0.1907);
MVP
0.61
MPC
0.30
ClinPred
0.091
T
GERP RS
3.7
Varity_R
0.11
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: chr4-55139764; API