rs246388

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002609.4(PDGFRB):c.3252A>G(p.Pro1084=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,611,204 control chromosomes in the GnomAD database, including 134,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10631 hom., cov: 33)

Exomes 𝑓: 0.40 ( 123688 hom. )

Consequence

PDGFRB
NM_002609.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.13

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 5-150115832-T-C is Benign according to our data. Variant chr5-150115832-T-C is described in ClinVar as [Benign]. Clinvar id is 258779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150115832-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDGFRB	NM_002609.4 linkuse as main transcript	c.3252A>G	p.Pro1084=	synonymous_variant	23/23	ENST00000261799.9
PDGFRB	NM_001355016.2 linkuse as main transcript	c.3060A>G	p.Pro1020=	synonymous_variant	22/22
PDGFRB	NM_001355017.2 linkuse as main transcript	c.2769A>G	p.Pro923=	synonymous_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9 linkuse as main transcript	c.3252A>G	p.Pro1084=	synonymous_variant	23/23	1	NM_002609.4	P1	P09619-1
PDGFRB	ENST00000520579.5 linkuse as main transcript	c.*2566A>G		3_prime_UTR_variant, NMD_transcript_variant	23/23	1

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55566

AN:

152086

Hom.:

10616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.379

GnomAD3 exomes

AF:

0.340

AC:

83370

AN:

245412

Hom.:

15551

AF XY:

0.347

AC XY:

46145

AN XY:

133048

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.247

Gnomad ASJ exome

AF:

0.420

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.404

AC:

589752

AN:

1459000

Hom.:

123688

Cov.:

AF XY:

0.403

AC XY:

292118

AN XY:

725644

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.257

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.436

Gnomad4 OTH exome

AF:

0.394

GnomAD4 genome

AF:

0.365

AC:

55622

AN:

152204

Hom.:

10631

Cov.:

AF XY:

0.354

AC XY:

26307

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.325

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.433

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.410

Hom.:

6564

Bravo

AF:

0.366

Asia WGS

AF:

0.216

AC:

752

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Acroosteolysis-keloid-like lesions-premature aging syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Basal ganglia calcification, idiopathic, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Myeloproliferative disorder, chronic, with eosinophilia

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

Cadd

Benign

0.13

Dann

Benign

0.19

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