5-150120109-T-C

Variant names:

Variant summary

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

The NM_002609.4(PDGFRB):c.2601A>G(p.Leu867Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,564,366 control chromosomes in the GnomAD database, including 75,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5805 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69199 hom. )

Consequence

PDGFRB
NM_002609.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.851

Publications

38 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 5-150120109-T-C is Benign according to our data. Variant chr5-150120109-T-C is described in ClinVar as Benign. ClinVar VariationId is 258776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.851 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PDGFRB	NM_002609.4 link	c.2601A>G	p.Leu867Leu	synonymous_variant	Exon 19 of 23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2 link	c.2409A>G	p.Leu803Leu	synonymous_variant	Exon 18 of 22		NP_001341945.1
PDGFRB	NM_001355017.2 link	c.2118A>G	p.Leu706Leu	synonymous_variant	Exon 19 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PDGFRB	ENST00000261799.9 link	c.2601A>G	p.Leu867Leu	synonymous_variant	Exon 19 of 23	1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5 link	n.*1915A>G		non_coding_transcript_exon_variant	Exon 19 of 23	1		ENSP00000430026.1
PDGFRB	ENST00000520579.5 link	n.*1915A>G		3_prime_UTR_variant	Exon 19 of 23	1		ENSP00000430026.1
PDGFRB	ENST00000519575.5 link	n.515A>G		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40665

AN:

151950

Hom.:

5791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.282

GnomAD2 exomes

AF:

0.286

AC:

71831

AN:

251184

AF XY:

0.292

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.308

AC:

435191

AN:

1412298

Hom.:

69199

Cov.:

AF XY:

0.310

AC XY:

218485

AN XY:

705368

show subpopulations

African (AFR)

AF:

0.165

AC:

5389

AN:

32708

American (AMR)

AF:

0.270

AC:

12054

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

8314

AN:

25802

East Asian (EAS)

AF:

0.138

AC:

5440

AN:

39496

South Asian (SAS)

AF:

0.334

AC:

28497

AN:

85330

European-Finnish (FIN)

AF:

0.211

AC:

11273

AN:

53330

Middle Eastern (MID)

AF:

0.369

AC:

2089

AN:

5660

European-Non Finnish (NFE)

AF:

0.323

AC:

344524

AN:

1066532

Other (OTH)

AF:

0.300

AC:

17611

AN:

58778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

13885

27769

41654

55538

69423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10802

21604

32406

43208

54010

<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:

0.268

AC:

40713

AN:

152068

Hom.:

5805

Cov.:

AF XY:

0.263

AC XY:

19521

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.174

AC:

7225

AN:

41470

American (AMR)

AF:

0.282

AC:

4315

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1121

AN:

3470

East Asian (EAS)

AF:

0.141

AC:

729

AN:

5166

South Asian (SAS)

AF:

0.338

AC:

1632

AN:

4822

European-Finnish (FIN)

AF:

0.209

AC:

2208

AN:

10582

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22514

AN:

67952

Other (OTH)

AF:

0.285

AC:

602

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1512

3025

4537

6050

7562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.309

Hom.:

15089

Bravo

AF:

0.262

EpiCase

AF:

0.329

EpiControl

AF:

0.335

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Genome Diagnostics Laboratory, Amsterdam University 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

PDGFRB-related disorder

Benign:1

Jun 08, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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 14, 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

-0.56

CADD

Benign

8.4

(source)

DANN

Benign

0.56

PhyloP100

0.85

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

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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