rs28489067

Variant names:

Variant summary

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

The NM_006206.6(PDGFRA):c.1121+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,592,174 control chromosomes in the GnomAD database, including 20,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2862 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17471 hom. )

Consequence

PDGFRA
NM_006206.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.929

Publications

4 publications found

Variant links:

COSMIC-nc: COSV99956060

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 4-54267769-C-T is Benign according to our data. Variant chr4-54267769-C-T is described in ClinVar as Benign. ClinVar VariationId is 259948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6 link	c.1121+28C>T		intron_variant	Intron 7 of 22	ENST00000257290.10	NP_006197.1	P16234-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDGFRA	ENST00000257290.10 link	c.1121+28C>T	intron_variant	Intron 7 of 22	1	NM_006206.6	ENSP00000257290.5	P16234-1
ENSG00000282278	ENST00000507166.5 link	c.1018-7156C>T	intron_variant	Intron 12 of 23	2		ENSP00000423325.1	A0A0B4J203
PDGFRA	ENST00000509092.5 link	n.939+28C>T	intron_variant	Intron 6 of 14	1
PDGFRA	ENST00000509490.5 link	n.1121+28C>T	intron_variant	Intron 7 of 17	1		ENSP00000424218.1	P16234-3

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26956

AN:

151944

Hom.:

2860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.0643

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.148

GnomAD2 exomes

AF:

0.184

AC:

45021

AN:

244462

AF XY:

0.175

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.408

Gnomad ASJ exome

AF:

0.0658

Gnomad EAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.143

AC:

205980

AN:

1440112

Hom.:

17471

Cov.:

AF XY:

0.143

AC XY:

102349

AN XY:

717736

show subpopulations

African (AFR)

AF:

0.248

AC:

8175

AN:

32982

American (AMR)

AF:

0.393

AC:

17495

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

1852

AN:

26034

East Asian (EAS)

AF:

0.167

AC:

6576

AN:

39474

South Asian (SAS)

AF:

0.220

AC:

18813

AN:

85658

European-Finnish (FIN)

AF:

0.121

AC:

6424

AN:

53084

Middle Eastern (MID)

AF:

0.0902

AC:

511

AN:

5666

European-Non Finnish (NFE)

AF:

0.126

AC:

137546

AN:

1093062

Other (OTH)

AF:

0.144

AC:

8588

AN:

59656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

7486

14972

22459

29945

37431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5306

10612

15918

21224

26530

<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:

0.177

AC:

26986

AN:

152062

Hom.:

2862

Cov.:

AF XY:

0.180

AC XY:

13372

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.248

AC:

10293

AN:

41430

American (AMR)

AF:

0.283

AC:

4325

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0643

AC:

223

AN:

3470

East Asian (EAS)

AF:

0.183

AC:

947

AN:

5172

South Asian (SAS)

AF:

0.246

AC:

1181

AN:

4808

European-Finnish (FIN)

AF:

0.125

AC:

1328

AN:

10600

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8284

AN:

67992

Other (OTH)

AF:

0.146

AC:

308

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1106

2211

3317

4422

5528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.135

Hom.:

325

Bravo

AF:

0.192

Asia WGS

AF:

0.240

AC:

834

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.94

(source)

DANN

Benign

0.81

PhyloP100

-0.93

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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