4-54267639-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006206.6(PDGFRA):c.1019G>A(p.Arg340Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,614,018 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R340W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.015 ( 55 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 52 hom. )

Consequence

PDGFRA
NM_006206.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:7O:1

Conservation

PhyloP100: 2.91

Publications

16 publications found

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]

PDGFRA Gene-Disease associations (from GenCC):

gastrointestinal stromal tumor
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
polyps, multiple and recurrent inflammatory fibroid, gastrointestinal
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
isolated cleft palate
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PDGFRA links:

ENSG00000282278 (HGNC:):

ENSG00000282278 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002336204).

BP6

Variant 4-54267639-G-A is Benign according to our data. Variant chr4-54267639-G-A is described in ClinVar as Benign. ClinVar VariationId is 41790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006206.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDGFRA	NM_006206.6	MANE Select	c.1019G>A	p.Arg340Gln	missense	Exon 7 of 23	NP_006197.1	P16234-1
PDGFRA	NM_001347828.2		c.1094G>A	p.Arg365Gln	missense	Exon 8 of 24	NP_001334757.1
PDGFRA	NM_001347830.2		c.1058G>A	p.Arg353Gln	missense	Exon 7 of 23	NP_001334759.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.1019G>A	p.Arg340Gln	missense	Exon 7 of 23	ENSP00000257290.5	P16234-1
ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-7286G>A		intron	N/A	ENSP00000423325.1	A0A0B4J203
PDGFRA	ENST00000509092.5	TSL:1	n.837G>A		non_coding_transcript_exon	Exon 6 of 15

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2285

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0516

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00405

AC:

1017

AN:

250864

AF XY:

0.00307

show subpopulations

Gnomad AFR exome

AF:

0.0546

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00158

AC:

2315

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

970

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0531

AC:

1777

AN:

33476

American (AMR)

AF:

0.00306

AC:

137

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000128

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000134

AC:

149

AN:

1111940

Other (OTH)

AF:

0.00379

AC:

229

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

121

242

362

483

604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0151

AC:

2293

AN:

152216

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1110

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0516

AC:

2142

AN:

41518

American (AMR)

AF:

0.00726

AC:

111

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68010

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

105

210

316

421

526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00612

Hom.:

Bravo

AF:

0.0173

ESP6500AA

AF:

0.0493

AC:

217

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00499

AC:

606

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Gastrointestinal stromal tumor (2)

Hereditary cancer-predisposing syndrome (1)

Idiopathic hypereosinophilic syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.076

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

PhyloP100

2.9

PrimateAI

Benign

0.25

PROVEAN

Benign

1.7

REVEL

Benign

0.12

Sift

Benign

0.32

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.029

MVP

0.28

MPC

0.37

ClinPred

0.0041

GERP RS

0.65

Varity_R

0.052

gMVP

0.18

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over