chr5-150129831-C-T

Position:

chr5-150129831-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002609.4(PDGFRB):c.1505G>A(p.Arg502Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,114 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R502W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 5 hom. )

Consequence

PDGFRB
NM_002609.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.940

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=0.004624516).

BP6

Variant 5-150129831-C-T is Benign according to our data. Variant chr5-150129831-C-T is described in ClinVar as [Benign]. Clinvar id is 473403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150129831-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00156 (237/152374) while in subpopulation NFE AF= 0.00228 (155/68042). AF 95% confidence interval is 0.00198. There are 0 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 237 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDGFRB	NM_002609.4 linkuse as main transcript	c.1505G>A	p.Arg502Gln	missense_variant	10/23	ENST00000261799.9
PDGFRB	NM_001355016.2 linkuse as main transcript	c.1313G>A	p.Arg438Gln	missense_variant	9/22
PDGFRB	NM_001355017.2 linkuse as main transcript	c.1022G>A	p.Arg341Gln	missense_variant	10/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9 linkuse as main transcript	c.1505G>A	p.Arg502Gln	missense_variant	10/23	1	NM_002609.4	P1	P09619-1
PDGFRB	ENST00000520579.5 linkuse as main transcript	c.*819G>A		3_prime_UTR_variant, NMD_transcript_variant	10/23	1

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00198

AC:

498

AN:

251254

Hom.:

AF XY:

0.00182

AC XY:

247

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00624

Gnomad NFE exome

AF:

0.00286

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00210

AC:

3067

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

1473

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00642

Gnomad4 NFE exome

AF:

0.00231

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00156

AC:

237

AN:

152374

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00111

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00212

AC:

257

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	PDGFRB: BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.24

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.82

M_CAP

Benign

0.032

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

0.56

REVEL

Benign

0.082

Sift

Benign

0.61

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.065

MVP

0.22

MPC

1.2

ClinPred

0.0083

GERP RS

1.4

Varity_R

0.025

gMVP

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