4-54274888-A-G

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.1701A>G(p.Pro567Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 1,613,940 control chromosomes in the GnomAD database, including 795,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P567P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.97 ( 71320 hom., cov: 31)

Exomes 𝑓: 1.0 ( 724115 hom. )

Consequence

PDGFRA
NM_006206.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -3.56

Publications

80 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=-0.98).

BP6

Variant 4-54274888-A-G is Benign according to our data. Variant chr4-54274888-A-G is described in ClinVar as Benign. ClinVar VariationId is 259949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.56 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6 link	c.1701A>G	p.Pro567Pro	synonymous_variant	Exon 12 of 23	ENST00000257290.10	NP_006197.1	P16234-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDGFRA	ENST00000257290.10 link	c.1701A>G	p.Pro567Pro	synonymous_variant	Exon 12 of 23	1	NM_006206.6	ENSP00000257290.5	P16234-1
PDGFRA	ENST00000509092.5 link	n.1519A>G		non_coding_transcript_exon_variant	Exon 11 of 15	1
PDGFRA	ENST00000509490.5 link	n.1701A>G		non_coding_transcript_exon_variant	Exon 12 of 18	1		ENSP00000424218.1	P16234-3
ENSG00000282278	ENST00000507166.5 link	c.1018-37A>G		intron_variant	Intron 12 of 23	2		ENSP00000423325.1	A0A0B4J203

Frequencies

GnomAD3 genomes

AF:

0.967

AC:

147117

AN:

152124

Hom.:

71292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

0.993

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.971

GnomAD2 exomes

AF:

0.990

AC:

248680

AN:

251180

AF XY:

0.992

show subpopulations

Gnomad AFR exome

AF:

0.885

Gnomad AMR exome

AF:

0.991

Gnomad ASJ exome

AF:

0.994

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

AF:

0.995

AC:

1454661

AN:

1461698

Hom.:

724115

Cov.:

AF XY:

0.996

AC XY:

723988

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.877

AC:

29369

AN:

33474

American (AMR)

AF:

0.990

AC:

44272

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.993

AC:

25966

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39699

AN:

39700

South Asian (SAS)

AF:

0.999

AC:

86208

AN:

86258

European-Finnish (FIN)

AF:

1.00

AC:

53413

AN:

53416

Middle Eastern (MID)

AF:

0.985

AC:

5681

AN:

5768

European-Non Finnish (NFE)

AF:

0.999

AC:

1110410

AN:

1111836

Other (OTH)

AF:

0.988

AC:

59643

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

373

745

1118

1490

1863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21662

43324

64986

86648

108310

<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:

0.967

AC:

147194

AN:

152242

Hom.:

71320

Cov.:

AF XY:

0.968

AC XY:

72095

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.889

AC:

36916

AN:

41522

American (AMR)

AF:

0.985

AC:

15055

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.993

AC:

3445

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5159

AN:

5160

South Asian (SAS)

AF:

0.999

AC:

4813

AN:

4818

European-Finnish (FIN)

AF:

1.00

AC:

10618

AN:

10618

Middle Eastern (MID)

AF:

0.980

AC:

288

AN:

294

European-Non Finnish (NFE)

AF:

0.998

AC:

67935

AN:

68044

Other (OTH)

AF:

0.971

AC:

2053

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

227

453

680

906

1133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.984

Hom.:

64981

Bravo

AF:

0.961

Asia WGS

AF:

0.986

AC:

3430

AN:

3478

EpiCase

AF:

0.998

EpiControl

AF:

0.998

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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

Jan 12, 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

- -

Idiopathic hypereosinophilic syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Carcinoma of colon

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant was identified in the 1000 Genomes Project in 80 of 2162 chromosomes (frequency: 0.037), Exome Variant Server project in 8587 of 9122 European American and in 3884 of 4406 African American alleles, increasing the likelihood that this is/may be a low frequency benign variant in certain populations of origin. The p.Pro567Pro variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site.In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. -

Squamous cell lung carcinoma

Benign:1

May 05, 2020

Faculté Pluridciplinaire Nador, Université Mohamed Premier

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing;in vivo

- -

Hereditary cancer-predisposing syndrome

Benign:1

Sep 13, 2018

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

-0.98

CADD

Benign

0.093

(source)

DANN

Benign

0.40

PhyloP100

-3.6

Mutation Taster

=67/33

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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