rs56072663

Positions:

chr5-150124785-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002609.4(PDGFRB):c.1854G>A(p.Thr618=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,609,566 control chromosomes in the GnomAD database, including 1,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 91 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1061 hom. )

Consequence

PDGFRB
NM_002609.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.17

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=-0.42).

BP6

Variant 5-150124785-C-T is Benign according to our data. Variant chr5-150124785-C-T is described in ClinVar as [Benign]. Clinvar id is 473404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150124785-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PDGFRB	NM_002609.4 linkuse as main transcript	c.1854G>A	p.Thr618=	synonymous_variant	13/23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2 linkuse as main transcript	c.1662G>A	p.Thr554=	synonymous_variant	12/22		NP_001341945.1
PDGFRB	NM_001355017.2 linkuse as main transcript	c.1371G>A	p.Thr457=	synonymous_variant	13/23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9 linkuse as main transcript	c.1854G>A	p.Thr618=	synonymous_variant	13/23	1	NM_002609.4	ENSP00000261799	P1	P09619-1
PDGFRB	ENST00000520579.5 linkuse as main transcript	c.*1168G>A		3_prime_UTR_variant, NMD_transcript_variant	13/23	1		ENSP00000430026
PDGFRB	ENST00000520229.1 linkuse as main transcript	n.123G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0254

AC:

3869

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00585

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0806

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0580

Gnomad FIN

AF:

0.0157

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0326

GnomAD3 exomes

AF:

0.0315

AC:

7833

AN:

248748

Hom.:

232

AF XY:

0.0349

AC XY:

4710

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.00540

Gnomad AMR exome

AF:

0.0169

Gnomad ASJ exome

AF:

0.0795

Gnomad EAS exome

AF:

0.000273

Gnomad SAS exome

AF:

0.0566

Gnomad FIN exome

AF:

0.0160

Gnomad NFE exome

AF:

0.0363

Gnomad OTH exome

AF:

0.0357

GnomAD4 exome

AF:

0.0327

AC:

47729

AN:

1457398

Hom.:

1061

Cov.:

AF XY:

0.0343

AC XY:

24859

AN XY:

725178

show subpopulations

Gnomad4 AFR exome

AF:

0.00569

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.0812

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0585

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0326

Gnomad4 OTH exome

AF:

0.0343

GnomAD4 genome

AF:

0.0254

AC:

3869

AN:

152168

Hom.:

Cov.:

AF XY:

0.0247

AC XY:

1836

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00583

Gnomad4 AMR

AF:

0.0231

Gnomad4 ASJ

AF:

0.0806

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0583

Gnomad4 FIN

AF:

0.0157

Gnomad4 NFE

AF:

0.0361

Gnomad4 OTH

AF:

0.0323

Alfa

AF:

0.0349

Hom.:

Bravo

AF:

0.0238

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0402

EpiControl

AF:

0.0427

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 06, 2018

- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.1

DANN

Benign

0.74

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