chr4-54273604-T-C

Variant names:

Variant summary

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

The NM_001347828.2(PDGFRA):c.1507T>C(p.Ser503Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,404 control chromosomes in the GnomAD database, including 14,579 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. S503F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.15 ( 2161 hom., cov: 31)

Exomes 𝑓: 0.12 ( 12418 hom. )

Consequence

PDGFRA
NM_001347828.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:8O:1

Conservation

PhyloP100: -1.15

Publications

87 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077081323).

BP6

Variant 4-54273604-T-C is Benign according to our data. Variant chr4-54273604-T-C is described in ClinVar as Benign. ClinVar VariationId is 41794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347828.2. 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.1432T>C	p.Ser478Pro	missense	Exon 10 of 23	NP_006197.1
PDGFRA	NM_001347828.2		c.1507T>C	p.Ser503Pro	missense	Exon 11 of 24	NP_001334757.1
PDGFRA	NM_001347830.2		c.1471T>C	p.Ser491Pro	missense	Exon 10 of 23	NP_001334759.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.1432T>C	p.Ser478Pro	missense	Exon 10 of 23	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-1321T>C		intron	N/A	ENSP00000423325.1
PDGFRA	ENST00000509092.5	TSL:1	n.1250T>C		non_coding_transcript_exon	Exon 9 of 15

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23418

AN:

151798

Hom.:

2161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.127

GnomAD2 exomes

AF:

0.154

AC:

38733

AN:

251048

AF XY:

0.150

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.0579

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.122

AC:

177975

AN:

1461488

Hom.:

12418

Cov.:

AF XY:

0.122

AC XY:

89046

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.230

AC:

7704

AN:

33472

American (AMR)

AF:

0.275

AC:

12289

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0629

AC:

1644

AN:

26132

East Asian (EAS)

AF:

0.142

AC:

5632

AN:

39700

South Asian (SAS)

AF:

0.205

AC:

17665

AN:

86252

European-Finnish (FIN)

AF:

0.121

AC:

6430

AN:

53278

Middle Eastern (MID)

AF:

0.0850

AC:

490

AN:

5768

European-Non Finnish (NFE)

AF:

0.107

AC:

118876

AN:

1111782

Other (OTH)

AF:

0.120

AC:

7245

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

8104

16208

24312

32416

40520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4618

9236

13854

18472

23090

<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:

0.154

AC:

23436

AN:

151916

Hom.:

2161

Cov.:

AF XY:

0.157

AC XY:

11659

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.229

AC:

9492

AN:

41382

American (AMR)

AF:

0.202

AC:

3090

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0562

AC:

195

AN:

3472

East Asian (EAS)

AF:

0.143

AC:

737

AN:

5142

South Asian (SAS)

AF:

0.228

AC:

1098

AN:

4806

European-Finnish (FIN)

AF:

0.127

AC:

1344

AN:

10582

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7106

AN:

67950

Other (OTH)

AF:

0.126

AC:

265

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

873

1746

2620

3493

4366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.125

Hom.:

3942

Bravo

AF:

0.163

TwinsUK

AF:

0.111

AC:

413

ALSPAC

AF:

0.109

AC:

420

ESP6500AA

AF:

0.226

AC:

995

ESP6500EA

AF:

0.103

AC:

882

ExAC

AF:

0.151

AC:

18396

Asia WGS

AF:

0.210

AC:

729

AN:

3478

EpiCase

AF:

0.100

EpiControl

AF:

0.0983

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Gastrointestinal stromal tumor (2)

Hereditary cancer-predisposing syndrome (1)

Idiopathic hypereosinophilic syndrome (1)

Myeloproliferative neoplasm, unclassifiable (1)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.0

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.080

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.071

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

PhyloP100

-1.2

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.16

REVEL

Benign

0.088

Sift

Benign

0.30

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.065

MPC

0.41

ClinPred

0.0012

GERP RS

0.81

Varity_R

0.078

gMVP

0.63

Mutation Taster

=95/5

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

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

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