chr4-54277410-G-A

Variant names:

Variant summary

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

The NM_006206.6(PDGFRA):c.1809G>A(p.Ala603Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,612,388 control chromosomes in the GnomAD database, including 16,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3008 hom., cov: 31)

Exomes 𝑓: 0.12 ( 13005 hom. )

Consequence

PDGFRA
NM_006206.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.22

Publications

25 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=-0.8).

BP6

Variant 4-54277410-G-A is Benign according to our data. Variant chr4-54277410-G-A is described in ClinVar as Benign. ClinVar VariationId is 259950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6 link	c.1809G>A	p.Ala603Ala	synonymous_variant	Exon 13 of 23	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10 link	c.1809G>A	p.Ala603Ala	synonymous_variant	Exon 13 of 23	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5 link	c.1089G>A	p.Ala363Ala	synonymous_variant	Exon 14 of 24	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26546

AN:

151862

Hom.:

3009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.145

GnomAD2 exomes

AF:

0.159

AC:

40099

AN:

251462

AF XY:

0.153

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.302

Gnomad ASJ exome

AF:

0.0583

Gnomad EAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.121

AC:

176694

AN:

1460408

Hom.:

13005

Cov.:

AF XY:

0.121

AC XY:

88234

AN XY:

726574

show subpopulations

African (AFR)

AF:

0.308

AC:

10289

AN:

33428

American (AMR)

AF:

0.290

AC:

12985

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0633

AC:

1653

AN:

26132

East Asian (EAS)

AF:

0.144

AC:

5718

AN:

39686

South Asian (SAS)

AF:

0.208

AC:

17971

AN:

86212

European-Finnish (FIN)

AF:

0.109

AC:

5847

AN:

53418

Middle Eastern (MID)

AF:

0.0827

AC:

477

AN:

5766

European-Non Finnish (NFE)

AF:

0.103

AC:

114429

AN:

1110716

Other (OTH)

AF:

0.121

AC:

7325

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

7840

15680

23519

31359

39199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4504

9008

13512

18016

22520

<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:

0.175

AC:

26560

AN:

151980

Hom.:

3008

Cov.:

AF XY:

0.177

AC XY:

13117

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.305

AC:

12643

AN:

41392

American (AMR)

AF:

0.215

AC:

3283

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0545

AC:

189

AN:

3468

East Asian (EAS)

AF:

0.145

AC:

744

AN:

5134

South Asian (SAS)

AF:

0.232

AC:

1114

AN:

4810

European-Finnish (FIN)

AF:

0.117

AC:

1240

AN:

10584

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6929

AN:

67990

Other (OTH)

AF:

0.143

AC:

302

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1042

2084

3126

4168

5210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.131

Hom.:

971

Bravo

AF:

0.187

Asia WGS

AF:

0.200

AC:

696

AN:

3478

EpiCase

AF:

0.0973

EpiControl

AF:

0.0957

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Gastrointestinal stromal tumor

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Idiopathic hypereosinophilic syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hereditary cancer-predisposing syndrome

Benign:1

May 08, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.1

(source)

DANN

Benign

0.76

PhyloP100

-5.2

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over