rs17110944

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002609.4(PDGFRB):c.85A>T(p.Ile29Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,547,842 control chromosomes in the GnomAD database, including 2,111 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 1000 hom., cov: 33)

Exomes 𝑓: 0.012 ( 1111 hom. )

Consequence

PDGFRB
NM_002609.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.173

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034821332).

BP6

Variant 5-150135834-T-A is Benign according to our data. Variant chr5-150135834-T-A is described in ClinVar as [Benign]. Clinvar id is 258780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150135834-T-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4 link	c.85A>T	p.Ile29Phe	missense_variant	Exon 3 of 23	ENST00000261799.9	NP_002600.1	P09619-1Q59F04
PDGFRB	NM_001355016.2 link	c.-108A>T		5_prime_UTR_variant	Exon 2 of 22		NP_001341945.1
PDGFRB	NM_001355017.2 link	c.-433A>T		5_prime_UTR_variant	Exon 3 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDGFRB	ENST00000261799.9 link	c.85A>T	p.Ile29Phe	missense_variant	Exon 3 of 23	1	NM_002609.4	ENSP00000261799.4	P09619-1
PDGFRB	ENST00000520579.5 link	n.85A>T		non_coding_transcript_exon_variant	Exon 3 of 23	1		ENSP00000430026.1	E5RH16
PDGFRB	ENST00000517957.1 link	c.85A>T	p.Ile29Phe	missense_variant	Exon 3 of 4	4		ENSP00000430715.1	E5RII0
PDGFRB	ENST00000517488.1 link	c.-108A>T		5_prime_UTR_variant	Exon 2 of 3	3		ENSP00000429218.1	E5RJ14

Frequencies

GnomAD3 genomes

AF:

0.0680

AC:

10334

AN:

152020

Hom.:

990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0558

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.0606

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0381

AC:

7455

AN:

195908

Hom.:

540

AF XY:

0.0315

AC XY:

3281

AN XY:

104086

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.0880

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0316

Gnomad SAS exome

AF:

0.0530

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.0219

GnomAD4 exome

AF:

0.0124

AC:

17254

AN:

1395704

Hom.:

1111

Cov.:

AF XY:

0.0125

AC XY:

8603

AN XY:

687500

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.0837

Gnomad4 ASJ exome

AF:

0.0000922

Gnomad4 EAS exome

AF:

0.0246

Gnomad4 SAS exome

AF:

0.0501

Gnomad4 FIN exome

AF:

0.0155

Gnomad4 NFE exome

AF:

0.000697

Gnomad4 OTH exome

AF:

0.0233

GnomAD4 genome

AF:

0.0682

AC:

10383

AN:

152138

Hom.:

1000

Cov.:

AF XY:

0.0671

AC XY:

4990

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.0561

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0363

Gnomad4 SAS

AF:

0.0600

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.0431

Alfa

AF:

0.0295

Hom.:

Bravo

AF:

0.0770

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.212

AC:

933

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0377

AC:

4561

Asia WGS

AF:

0.0750

AC:

260

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 20, 2019

GeneDx

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). -

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

0.072

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.66

DANN

Benign

0.73

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.81

N;N

REVEL

Benign

0.019

Sift

Benign

0.33

T;T

Sift4G

Benign

0.42

T;.

Polyphen

0.022

B;.

Vest4

0.059

MPC

0.36

ClinPred

0.00030

GERP RS

-1.5

Varity_R

0.060

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over