rs2228440

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002609.4(PDGFRB):c.3090C>T(p.Pro1030Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 1,613,136 control chromosomes in the GnomAD database, including 8,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 628 hom., cov: 31)

Exomes 𝑓: 0.098 ( 7744 hom. )

Consequence

PDGFRB
NM_002609.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -4.01

Publications

17 publications found

Variant links:

Genes affected

PDGFRB (HGNC:8804): (platelet derived growth factor receptor beta) The protein encoded by this gene is 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 (PDGFB or PDGFD) or a heterodimer (PDGFA and PDGFB). This gene is essential for normal development of the cardiovascular system and aids in rearrangement of the actin cytoskeleton. This gene is flanked on chromosome 5 by the genes for granulocyte-macrophage colony-stimulating factor and macrophage-colony stimulating factor receptor; all three genes may be implicated in the 5-q syndrome. A translocation between chromosomes 5 and 12, that fuses this gene to that of the ETV6 gene, results in chronic myeloproliferative disorder with eosinophilia. [provided by RefSeq, Aug 2017]

PDGFRB Gene-Disease associations (from GenCC):

acroosteolysis-keloid-like lesions-premature aging syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
myofibromatosis, infantile, 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
basal ganglia calcification, idiopathic, 4
Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
bilateral striopallidodentate calcinosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
infantile myofibromatosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary progressive mucinous histiocytosis
Inheritance: AD Classification: LIMITED Submitted by: G2P

PDGFRB 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 5-150117665-G-A is Benign according to our data. Variant chr5-150117665-G-A is described in ClinVar as Benign. ClinVar VariationId is 258777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4 link	c.3090C>T	p.Pro1030Pro	synonymous_variant	Exon 22 of 23	ENST00000261799.9	NP_002600.1	P09619-1Q59F04
PDGFRB	NM_001355016.2 link	c.2898C>T	p.Pro966Pro	synonymous_variant	Exon 21 of 22		NP_001341945.1
PDGFRB	NM_001355017.2 link	c.2607C>T	p.Pro869Pro	synonymous_variant	Exon 22 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDGFRB	ENST00000261799.9 link	c.3090C>T	p.Pro1030Pro	synonymous_variant	Exon 22 of 23	1	NM_002609.4	ENSP00000261799.4	P09619-1
PDGFRB	ENST00000520579.5 link	n.*2404C>T		non_coding_transcript_exon_variant	Exon 22 of 23	1		ENSP00000430026.1	E5RH16
PDGFRB	ENST00000520579.5 link	n.*2404C>T		3_prime_UTR_variant	Exon 22 of 23	1		ENSP00000430026.1	E5RH16

Frequencies

GnomAD3 genomes

AF:

0.0882

AC:

13399

AN:

151928

Hom.:

629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0851

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0864

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0415

Gnomad FIN

AF:

0.0462

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0858

GnomAD2 exomes

AF:

0.0763

AC:

19165

AN:

251228

AF XY:

0.0771

show subpopulations

Gnomad AFR exome

AF:

0.0853

Gnomad AMR exome

AF:

0.0587

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0550

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.0821

GnomAD4 exome

AF:

0.0981

AC:

143318

AN:

1461090

Hom.:

7744

Cov.:

AF XY:

0.0966

AC XY:

70209

AN XY:

726890

show subpopulations

African (AFR)

AF:

0.0838

AC:

2803

AN:

33468

American (AMR)

AF:

0.0609

AC:

2723

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2877

AN:

26134

East Asian (EAS)

AF:

0.000227

AC:

AN:

39694

South Asian (SAS)

AF:

0.0387

AC:

3336

AN:

86240

European-Finnish (FIN)

AF:

0.0600

AC:

3207

AN:

53410

Middle Eastern (MID)

AF:

0.0826

AC:

476

AN:

5764

European-Non Finnish (NFE)

AF:

0.110

AC:

121992

AN:

1111298

Other (OTH)

AF:

0.0976

AC:

5895

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

6334

12667

19001

25334

31668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4448

8896

13344

17792

22240

<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:

0.0881

AC:

13398

AN:

152046

Hom.:

628

Cov.:

AF XY:

0.0840

AC XY:

6240

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0850

AC:

3523

AN:

41466

American (AMR)

AF:

0.0863

AC:

1318

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

402

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.0417

AC:

201

AN:

4820

European-Finnish (FIN)

AF:

0.0462

AC:

488

AN:

10574

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7172

AN:

67970

Other (OTH)

AF:

0.0849

AC:

179

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

633

1266

1900

2533

3166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.0999

Hom.:

807

Bravo

AF:

0.0913

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.108

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Acroosteolysis-keloid-like lesions-premature aging syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Basal ganglia calcification, idiopathic, 4

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Myofibromatosis, infantile, 1

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Myeloproliferative disorder, chronic, with eosinophilia

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Infantile myofibromatosis;C1866182:Acroosteolysis-keloid-like lesions-premature aging syndrome;C3554321:Basal ganglia calcification, idiopathic, 4;C4225270:Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.78

(source)

DANN

Benign

0.81

PhyloP100

-4.0

Mutation Taster

=99/1

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over