5-150129883-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002609.4(PDGFRB):c.1453G>A(p.Glu485Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,614,120 control chromosomes in the GnomAD database, including 484 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 48 hom., cov: 33)

Exomes 𝑓: 0.023 ( 436 hom. )

Consequence

PDGFRB
NM_002609.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.05

Publications

19 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 (MetaRNN=0.0025401115).

BP6

Variant 5-150129883-C-T is Benign according to our data. Variant chr5-150129883-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 473402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0195 (2969/152378) while in subpopulation NFE AF = 0.0281 (1909/68038). AF 95% confidence interval is 0.027. There are 48 homozygotes in GnomAd4. There are 1418 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2969 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PDGFRB	NM_002609.4 link	c.1453G>A	p.Glu485Lys	missense_variant	Exon 10 of 23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2 link	c.1261G>A	p.Glu421Lys	missense_variant	Exon 9 of 22		NP_001341945.1
PDGFRB	NM_001355017.2 link	c.970G>A	p.Glu324Lys	missense_variant	Exon 10 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PDGFRB	ENST00000261799.9 link	c.1453G>A	p.Glu485Lys	missense_variant	Exon 10 of 23	1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5 link	n.*767G>A		non_coding_transcript_exon_variant	Exon 10 of 23	1		ENSP00000430026.1
PDGFRB	ENST00000520579.5 link	n.*767G>A		3_prime_UTR_variant	Exon 10 of 23	1		ENSP00000430026.1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2968

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00583

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0264

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0280

Gnomad OTH

AF:

0.0272

GnomAD2 exomes

AF:

0.0195

AC:

4912

AN:

251424

AF XY:

0.0200

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0293

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.0285

Gnomad OTH exome

AF:

0.0246

GnomAD4 exome

AF:

0.0232

AC:

33982

AN:

1461742

Hom.:

436

Cov.:

AF XY:

0.0229

AC XY:

16657

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.00469

AC:

157

AN:

33478

American (AMR)

AF:

0.0179

AC:

801

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0275

AC:

718

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00897

AC:

774

AN:

86258

European-Finnish (FIN)

AF:

0.0141

AC:

750

AN:

53378

Middle Eastern (MID)

AF:

0.0369

AC:

213

AN:

5768

European-Non Finnish (NFE)

AF:

0.0263

AC:

29235

AN:

1111906

Other (OTH)

AF:

0.0221

AC:

1332

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1841

3682

5522

7363

9204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1044

2088

3132

4176

5220

<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:

0.0195

AC:

2969

AN:

152378

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1418

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.00582

AC:

242

AN:

41598

American (AMR)

AF:

0.0263

AC:

403

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00870

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0138

AC:

147

AN:

10630

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0281

AC:

1909

AN:

68038

Other (OTH)

AF:

0.0269

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

154

308

463

617

771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0254

Hom.:

139

Bravo

AF:

0.0212

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0223

AC:

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0260

AC:

224

ExAC

AF:

0.0187

AC:

2265

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0341

EpiControl

AF:

0.0347

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

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

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Oct 12, 2023

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria.

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

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.078

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

PhyloP100

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.77

REVEL

Benign

0.10

Sift

Benign

0.54

Sift4G

Benign

0.74

Vest4

0.19

ClinPred

0.010

GERP RS

3.7

Varity_R

0.22

gMVP

0.38

Mutation Taster

=97/3

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