4-54281602-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001347827.2(PDGFRA):c.2345C>T(p.Thr782Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,352,558 control chromosomes in the GnomAD database, including 5,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 583 hom., cov: 33)

Exomes 𝑓: 0.086 ( 4759 hom. )

Consequence

PDGFRA
NM_001347827.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:3O:1

Conservation

PhyloP100: 0.275

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 4-54281602-C-T is Benign according to our data. Variant chr4-54281602-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 133374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347827.2. 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.2323+1120C>T		intron	N/A	NP_006197.1	P16234-1
PDGFRA	NM_001347827.2		c.2345C>T	p.Thr782Met	missense	Exon 17 of 17	NP_001334756.1
PDGFRA	NM_001347828.2		c.2398+1120C>T		intron	N/A	NP_001334757.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.2323+1120C>T	intron	N/A	ENSP00000257290.5	P16234-1
ENSG00000282278	ENST00000507166.5	TSL:2	c.1603+1120C>T	intron	N/A	ENSP00000423325.1	A0A0B4J203
PDGFRA	ENST00000507536.1	TSL:1	n.771C>T	non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0839

AC:

12757

AN:

152112

Hom.:

582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0829

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.0594

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.0730

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0922

Gnomad OTH

AF:

0.102

GnomAD2 exomes

AF:

0.0725

AC:

9713

AN:

134042

AF XY:

0.0711

show subpopulations

Gnomad AFR exome

AF:

0.0855

Gnomad AMR exome

AF:

0.0543

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.0523

Gnomad FIN exome

AF:

0.0743

Gnomad NFE exome

AF:

0.0921

Gnomad OTH exome

AF:

0.0932

GnomAD4 exome

AF:

0.0862

AC:

103495

AN:

1200328

Hom.:

4759

Cov.:

AF XY:

0.0844

AC XY:

49542

AN XY:

587084

show subpopulations

African (AFR)

AF:

0.0850

AC:

2320

AN:

27282

American (AMR)

AF:

0.0557

AC:

1674

AN:

30076

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

2258

AN:

19956

East Asian (EAS)

AF:

0.0726

AC:

1622

AN:

22354

South Asian (SAS)

AF:

0.0329

AC:

2523

AN:

76680

European-Finnish (FIN)

AF:

0.0761

AC:

998

AN:

13110

Middle Eastern (MID)

AF:

0.110

AC:

524

AN:

4762

European-Non Finnish (NFE)

AF:

0.0913

AC:

87613

AN:

959316

Other (OTH)

AF:

0.0847

AC:

3963

AN:

46792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

4191

8382

12573

16764

20955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3612

7224

10836

14448

18060

<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:

0.0839

AC:

12769

AN:

152230

Hom.:

583

Cov.:

AF XY:

0.0824

AC XY:

6136

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0830

AC:

3445

AN:

41526

American (AMR)

AF:

0.0721

AC:

1103

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

403

AN:

3470

East Asian (EAS)

AF:

0.0599

AC:

310

AN:

5172

South Asian (SAS)

AF:

0.0284

AC:

137

AN:

4826

European-Finnish (FIN)

AF:

0.0730

AC:

774

AN:

10596

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0921

AC:

6268

AN:

68020

Other (OTH)

AF:

0.102

AC:

216

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

624

1248

1872

2496

3120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0894

Hom.:

1183

Bravo

AF:

0.0850

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary cancer (1)

Myeloproliferative neoplasm, unclassifiable (1)

not specified (2)

PDGFRA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.4

(source)

DANN

Benign

0.50

PhyloP100

0.28

Mutation Taster

=100/0

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

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