rs36035373

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.236G>A(p.Gly79Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,614,138 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G79S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0087 ( 9 hom., cov: 31)

Exomes 𝑓: 0.013 ( 143 hom. )

Consequence

PDGFRA
NM_006206.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: 7.65

Publications

38 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074451566).

BP6

Variant 4-54261281-G-A is Benign according to our data. Variant chr4-54261281-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 41797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1325 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
PDGFRA	NM_006206.6	MANE Select	c.236G>A	p.Gly79Asp	missense	Exon 3 of 23	NP_006197.1
PDGFRA	NM_001347828.2		c.311G>A	p.Gly104Asp	missense	Exon 4 of 24	NP_001334757.1
PDGFRA	NM_001347830.2		c.275G>A	p.Gly92Asp	missense	Exon 3 of 23	NP_001334759.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.236G>A	p.Gly79Asp	missense	Exon 3 of 23	ENSP00000257290.5
PDGFRA	ENST00000508170.5	TSL:1	c.236G>A	p.Gly79Asp	missense	Exon 3 of 4	ENSP00000425648.1
PDGFRA	ENST00000509490.5	TSL:1	n.236G>A		non_coding_transcript_exon	Exon 3 of 18	ENSP00000424218.1

Frequencies

GnomAD3 genomes

AF:

0.00871

AC:

1325

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00888

AC:

2233

AN:

251366

AF XY:

0.00935

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0127

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0127

AC:

18505

AN:

1461866

Hom.:

143

Cov.:

AF XY:

0.0126

AC XY:

9141

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00194

AC:

AN:

33478

American (AMR)

AF:

0.00259

AC:

116

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

316

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00356

AC:

307

AN:

86258

European-Finnish (FIN)

AF:

0.0134

AC:

715

AN:

53420

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0147

AC:

16332

AN:

1111988

Other (OTH)

AF:

0.0103

AC:

623

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1000

2001

3001

4002

5002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.00870

AC:

1325

AN:

152272

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

621

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

41554

American (AMR)

AF:

0.00346

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00394

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0137

AC:

145

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

960

AN:

68020

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00763

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0137

AC:

118

ExAC

AF:

0.00875

AC:

1062

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0150

EpiControl

AF:

0.0130

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 13, 2012

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:research

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PDGFRA: BS1, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Mar 22, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 28192086, 19755855, 24728327, 22703879, 17344846, 29205322)

Hereditary cancer-predisposing syndrome

Benign:3

Mar 26, 2019

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Jan 29, 2016

Vantari Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 11, 2021

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

Gastrointestinal stromal tumor

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1Other:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

Idiopathic hypereosinophilic syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

PhyloP100

7.7

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.31

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.021

Polyphen

0.99

Vest4

0.87

MVP

0.42

MPC

1.2

ClinPred

0.018

GERP RS

6.0

Varity_R

0.37

gMVP

0.88

Mutation Taster

=73/27

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over