rs61735626

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006206.6(PDGFRA):c.2230C>T(p.Pro744Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000424 in 1,611,340 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P744P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

PDGFRA
NM_006206.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 5.85

Publications

9 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013420343).

BP6

Variant 4-54280389-C-T is Benign according to our data. Variant chr4-54280389-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 135015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 297 AD,Unknown gene.

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.2230C>T	p.Pro744Ser	missense	Exon 16 of 23	NP_006197.1	P16234-1
PDGFRA	NM_001347828.2		c.2305C>T	p.Pro769Ser	missense	Exon 17 of 24	NP_001334757.1
PDGFRA	NM_001347830.2		c.2269C>T	p.Pro757Ser	missense	Exon 16 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.2230C>T	p.Pro744Ser	missense	Exon 16 of 23	ENSP00000257290.5	P16234-1
ENSG00000282278	ENST00000507166.5	TSL:2	c.1510C>T	p.Pro504Ser	missense	Exon 17 of 24	ENSP00000423325.1	A0A0B4J203
PDGFRA	ENST00000507536.1	TSL:1	n.656C>T		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

296

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00681

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.000569

AC:

143

AN:

251114

AF XY:

0.000420

show subpopulations

Gnomad AFR exome

AF:

0.00757

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000265

AC:

386

AN:

1459104

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

169

AN XY:

726050

show subpopulations

African (AFR)

AF:

0.00951

AC:

318

AN:

33426

American (AMR)

AF:

0.000313

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109486

Other (OTH)

AF:

0.000680

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00195

AC:

297

AN:

152236

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00681

AC:

283

AN:

41536

American (AMR)

AF:

0.000262

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000416

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68014

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000678

Hom.:

Bravo

AF:

0.00236

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000651

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary cancer-predisposing syndrome (2)

not provided (2)

Gastrointestinal stromal tumor (1)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.084

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.1

PhyloP100

5.8

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.45

Sift

Uncertain

0.027

Sift4G

Benign

0.068

Polyphen

0.74

Vest4

0.63

MVP

0.49

MPC

0.79

ClinPred

0.026

GERP RS

4.0

Varity_R

0.19

gMVP

0.68

Mutation Taster

=48/52

disease causing

(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