rs149417689

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_StrongBS1BS2

The NM_002609.4(PDGFRB):c.3119G>T(p.Gly1040Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,610,362 control chromosomes in the GnomAD database, including 21 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 0.0054 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 11 hom. )

Consequence

PDGFRB
NM_002609.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.53

Publications

2 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=0.008083612).

BP6

Variant 5-150117636-C-A is Benign according to our data. Variant chr5-150117636-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 473406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00538 (818/152168) while in subpopulation AFR AF = 0.0189 (783/41528). AF 95% confidence interval is 0.0178. There are 10 homozygotes in GnomAd4. There are 397 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 818 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PDGFRB	NM_002609.4 link	c.3119G>T	p.Gly1040Val	missense_variant	Exon 22 of 23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2 link	c.2927G>T	p.Gly976Val	missense_variant	Exon 21 of 22		NP_001341945.1
PDGFRB	NM_001355017.2 link	c.2636G>T	p.Gly879Val	missense_variant	Exon 22 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PDGFRB	ENST00000261799.9 link	c.3119G>T	p.Gly1040Val	missense_variant	Exon 22 of 23	1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5 link	n.*2433G>T		non_coding_transcript_exon_variant	Exon 22 of 23	1		ENSP00000430026.1
PDGFRB	ENST00000520579.5 link	n.*2433G>T		3_prime_UTR_variant	Exon 22 of 23	1		ENSP00000430026.1

Frequencies

GnomAD3 genomes

AF:

0.00535

AC:

813

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000774

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00156

AC:

392

AN:

250670

AF XY:

0.00103

show subpopulations

Gnomad AFR exome

AF:

0.0205

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000543

AC:

792

AN:

1458194

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

313

AN XY:

725430

show subpopulations

African (AFR)

AF:

0.0186

AC:

621

AN:

33376

American (AMR)

AF:

0.000649

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.000479

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000929

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000280

AC:

AN:

1108886

Other (OTH)

AF:

0.00138

AC:

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00538

AC:

818

AN:

152168

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

397

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0189

AC:

783

AN:

41528

American (AMR)

AF:

0.00137

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000775

AC:

AN:

5158

South Asian (SAS)

AF:

0.000416

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00184

Hom.:

Bravo

AF:

0.00674

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00185

AC:

224

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 04, 2025

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

Jan 20, 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

0.076

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0081

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.6

PhyloP100

3.5

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

REVEL

Benign

0.18

Sift

Benign

0.064

Sift4G

Uncertain

0.018

Polyphen

0.32

Vest4

0.15

MVP

0.51

MPC

0.46

ClinPred

0.014

GERP RS

5.3

Varity_R

0.18

gMVP

0.29

Mutation Taster

=94/6

polymorphism

(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