chr4-54263898-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006206.6(PDGFRA):c.599C>G(p.Thr200Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000555 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T200T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 0 hom. )

Consequence

PDGFRA
NM_006206.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:8O:1

Conservation

PhyloP100: 4.90

Publications

13 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008408099).

BP6

Variant 4-54263898-C-G is Benign according to our data. Variant chr4-54263898-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 41800.

BS2

High AC in GnomAd4 at 121 Unknown,AD 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.599C>G	p.Thr200Ser	missense	Exon 4 of 23	NP_006197.1	P16234-1
PDGFRA	NM_001347828.2		c.674C>G	p.Thr225Ser	missense	Exon 5 of 24	NP_001334757.1
PDGFRA	NM_001347830.2		c.638C>G	p.Thr213Ser	missense	Exon 4 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.599C>G	p.Thr200Ser	missense	Exon 4 of 23	ENSP00000257290.5	P16234-1
PDGFRA	ENST00000508170.5	TSL:1	c.599C>G	p.Thr200Ser	missense	Exon 4 of 4	ENSP00000425648.1	P16234-2
ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-11027C>G		intron	N/A	ENSP00000423325.1	A0A0B4J203

Frequencies

GnomAD3 genomes

AF:

0.000796

AC:

121

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000737

AC:

185

AN:

250858

AF XY:

0.000745

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.000530

AC:

774

AN:

1461730

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

407

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000589

AC:

655

AN:

1111920

Other (OTH)

AF:

0.000431

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

121

162

202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000795

AC:

121

AN:

152218

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41522

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00132

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.00107

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000774

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Gastrointestinal stromal tumor (2)

Hereditary cancer-predisposing syndrome (2)

Idiopathic hypereosinophilic syndrome (1)

not specified (2)

PDGFRA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.026

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.51

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0084

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

4.9

PrimateAI

Benign

0.43

PROVEAN

Benign

1.4

REVEL

Benign

0.094

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.089

MutPred

0.52

Loss of methylation at K197 (P = 0.1394)

MVP

0.38

MPC

0.29

ClinPred

0.041

GERP RS

4.8

Varity_R

0.13

gMVP

0.58

Mutation Taster

=88/12

polymorphism

(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