Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000257290.10(PDGFRA):c.612T>C(p.Asn204Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,612,950 control chromosomes in the GnomAD database, including 20,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2986 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17984 hom. )

Consequence

PDGFRA
ENST00000257290.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.60

Publications

24 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: Genomics England PanelApp, Ambry Genetics, G2P
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-54263911-T-C is Benign according to our data. Variant chr4-54263911-T-C is described in ClinVar as Benign. ClinVar VariationId is 259955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000257290.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRA	NM_006206.6	MANE Select	c.612T>C	p.Asn204Asn	synonymous	Exon 4 of 23	NP_006197.1
PDGFRA	NM_001347828.2		c.687T>C	p.Asn229Asn	synonymous	Exon 5 of 24	NP_001334757.1
PDGFRA	NM_001347830.2		c.651T>C	p.Asn217Asn	synonymous	Exon 4 of 23	NP_001334759.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.612T>C	p.Asn204Asn	synonymous	Exon 4 of 23	ENSP00000257290.5
PDGFRA	ENST00000508170.5	TSL:1	c.612T>C	p.Asn204Asn	synonymous	Exon 4 of 4	ENSP00000425648.1
PDGFRA	ENST00000509092.5	TSL:1	n.430T>C		non_coding_transcript_exon	Exon 3 of 15

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27424

AN:

151930

Hom.:

2984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.0702

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.155

GnomAD2 exomes

AF:

0.186

AC:

46654

AN:

250530

AF XY:

0.177

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.0712

Gnomad EAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.144

AC:

210489

AN:

1460904

Hom.:

17984

Cov.:

AF XY:

0.144

AC XY:

104392

AN XY:

726808

show subpopulations

African (AFR)

AF:

0.253

AC:

8446

AN:

33448

American (AMR)

AF:

0.398

AC:

17771

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0764

AC:

1997

AN:

26132

East Asian (EAS)

AF:

0.166

AC:

6609

AN:

39696

South Asian (SAS)

AF:

0.220

AC:

18942

AN:

86224

European-Finnish (FIN)

AF:

0.121

AC:

6458

AN:

53362

Middle Eastern (MID)

AF:

0.0992

AC:

572

AN:

5766

European-Non Finnish (NFE)

AF:

0.127

AC:

140813

AN:

1111234

Other (OTH)

AF:

0.147

AC:

8881

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

8478

16956

25434

33912

42390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5450

10900

16350

21800

27250

<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:

0.181

AC:

27462

AN:

152046

Hom.:

2986

Cov.:

AF XY:

0.183

AC XY:

13635

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.254

AC:

10510

AN:

41450

American (AMR)

AF:

0.290

AC:

4432

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0702

AC:

243

AN:

3464

East Asian (EAS)

AF:

0.183

AC:

945

AN:

5164

South Asian (SAS)

AF:

0.247

AC:

1189

AN:

4814

European-Finnish (FIN)

AF:

0.126

AC:

1328

AN:

10566

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8393

AN:

67994

Other (OTH)

AF:

0.154

AC:

324

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1111

2222

3333

4444

5555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.149

Hom.:

1394

Bravo

AF:

0.195

Asia WGS

AF:

0.247

AC:

857

AN:

3478

EpiCase

AF:

0.116

EpiControl

AF:

0.114

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gastrointestinal stromal tumor (2)

not provided (2)

Hereditary cancer-predisposing syndrome (1)

Idiopathic hypereosinophilic syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.092

(source)

DANN

Benign

0.70

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs2229307

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over