5-150129883-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.1453G>A(p.Glu485Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,614,120 control chromosomes in the GnomAD database, including 484 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 48 hom., cov: 33)

Exomes 𝑓: 0.023 ( 436 hom. )

Consequence

PDGFRB
NM_002609.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.05

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=0.0025401115).

BP6

Variant 5-150129883-C-T is Benign according to our data. Variant chr5-150129883-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 473402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150129883-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0195 (2969/152378) while in subpopulation NFE AF= 0.0281 (1909/68038). AF 95% confidence interval is 0.027. There are 48 homozygotes in gnomad4. There are 1418 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd at 2968 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDGFRB	NM_002609.4 linkuse as main transcript	c.1453G>A	p.Glu485Lys	missense_variant	10/23	ENST00000261799.9
PDGFRB	NM_001355016.2 linkuse as main transcript	c.1261G>A	p.Glu421Lys	missense_variant	9/22
PDGFRB	NM_001355017.2 linkuse as main transcript	c.970G>A	p.Glu324Lys	missense_variant	10/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9 linkuse as main transcript	c.1453G>A	p.Glu485Lys	missense_variant	10/23	1	NM_002609.4	P1	P09619-1
PDGFRB	ENST00000520579.5 linkuse as main transcript	c.*767G>A		3_prime_UTR_variant, NMD_transcript_variant	10/23	1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2968

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00583

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0264

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00890

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0280

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.0195

AC:

4912

AN:

251424

Hom.:

AF XY:

0.0200

AC XY:

2720

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0293

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00872

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.0285

Gnomad OTH exome

AF:

0.0246

GnomAD4 exome

AF:

0.0232

AC:

33982

AN:

1461742

Hom.:

436

Cov.:

AF XY:

0.0229

AC XY:

16657

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00469

Gnomad4 AMR exome

AF:

0.0179

Gnomad4 ASJ exome

AF:

0.0275

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00897

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0221

GnomAD4 genome

AF:

0.0195

AC:

2969

AN:

152378

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1418

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.00582

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.0274

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.0138

Gnomad4 NFE

AF:

0.0281

Gnomad4 OTH

AF:

0.0269

Alfa

AF:

0.0269

Hom.:

101

Bravo

AF:

0.0212

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0223

AC:

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0260

AC:

224

ExAC

AF:

0.0187

AC:

2265

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0341

EpiControl

AF:

0.0347

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 12, 2023

See Variant Classification Assertion Criteria. -

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

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.078

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.95

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.77

REVEL

Benign

0.10

Sift

Benign

0.54

Sift4G

Benign

0.74

Polyphen

0.13

Vest4

0.19

MPC

0.29

ClinPred

0.010

GERP RS

3.7

Varity_R

0.22

gMVP

0.38

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