rs2228439

Positions:

chr5-150132073-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_002609.4(PDGFRB):c.1149G>C(p.Leu383=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,606,436 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 103 hom. )

Consequence

PDGFRB
NM_002609.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.593

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 5-150132073-C-G is Benign according to our data. Variant chr5-150132073-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 473400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150132073-C-G is described in Lovd as [Benign]. Variant chr5-150132073-C-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.593 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00775 (1180/152310) while in subpopulation NFE AF= 0.0116 (790/68026). AF 95% confidence interval is 0.0109. There are 5 homozygotes in gnomad4. There are 543 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1180 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDGFRB	NM_002609.4 linkuse as main transcript	c.1149G>C	p.Leu383=	synonymous_variant	8/23	ENST00000261799.9
PDGFRB	NM_001355016.2 linkuse as main transcript	c.957G>C	p.Leu319=	synonymous_variant	7/22
PDGFRB	NM_001355017.2 linkuse as main transcript	c.666G>C	p.Leu222=	synonymous_variant	8/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9 linkuse as main transcript	c.1149G>C	p.Leu383=	synonymous_variant	8/23	1	NM_002609.4	P1	P09619-1
PDGFRB	ENST00000520579.5 linkuse as main transcript	c.*463G>C		3_prime_UTR_variant, NMD_transcript_variant	8/23	1

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1180

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00777

AC:

1948

AN:

250762

Hom.:

AF XY:

0.00770

AC XY:

1044

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00325

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.00981

GnomAD4 exome

AF:

0.0107

AC:

15524

AN:

1454126

Hom.:

103

Cov.:

AF XY:

0.0104

AC XY:

7516

AN XY:

723928

show subpopulations

Gnomad4 AFR exome

AF:

0.00189

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.0206

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000430

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.00986

GnomAD4 genome

AF:

0.00775

AC:

1180

AN:

152310

Hom.:

Cov.:

AF XY:

0.00729

AC XY:

543

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00733

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0112

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	PDGFRB: BP4, BP7, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 2021	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

PDGFRB-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 02, 2019

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). -

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 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.0

DANN

Benign

0.58

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