5-150132931-C-T

Position:

chr5-150132931-C-T

Variant summary

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

The ENST00000261799.9(PDGFRB):c.946G>A(p.Val316Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 1,560,448 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 20 hom. )

Consequence

PDGFRB
ENST00000261799.9 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.995

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=0.0081400275).

BP6

Variant 5-150132931-C-T is Benign according to our data. Variant chr5-150132931-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 285888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150132931-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0028 (427/152392) while in subpopulation NFE AF= 0.00438 (298/68044). AF 95% confidence interval is 0.00397. There are 2 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 427 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PDGFRB	NM_002609.4 linkuse as main transcript	c.946G>A	p.Val316Met	missense_variant	7/23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2 linkuse as main transcript	c.754G>A	p.Val252Met	missense_variant	6/22		NP_001341945.1
PDGFRB	NM_001355017.2 linkuse as main transcript	c.463G>A	p.Val155Met	missense_variant	7/23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9 linkuse as main transcript	c.946G>A	p.Val316Met	missense_variant	7/23	1	NM_002609.4	ENSP00000261799	P1	P09619-1
PDGFRB	ENST00000520579.5 linkuse as main transcript	c.*260G>A		3_prime_UTR_variant, NMD_transcript_variant	7/23	1		ENSP00000430026

Frequencies

GnomAD3 genomes

AF:

0.00280

AC:

427

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.0158

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00438

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00332

AC:

558

AN:

167866

Hom.:

AF XY:

0.00302

AC XY:

269

AN XY:

89110

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00119

Gnomad FIN exome

AF:

0.00232

Gnomad NFE exome

AF:

0.00435

Gnomad OTH exome

AF:

0.00476

GnomAD4 exome

AF:

0.00334

AC:

4709

AN:

1408056

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

2290

AN XY:

695686

show subpopulations

Gnomad4 AFR exome

AF:

0.000311

Gnomad4 AMR exome

AF:

0.000924

Gnomad4 ASJ exome

AF:

0.0160

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000849

Gnomad4 FIN exome

AF:

0.00298

Gnomad4 NFE exome

AF:

0.00350

Gnomad4 OTH exome

AF:

0.00395

GnomAD4 genome

AF:

0.00280

AC:

427

AN:

152392

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

206

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.0158

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00263

Gnomad4 NFE

AF:

0.00438

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00424

Hom.:

Bravo

AF:

0.00241

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00455

AC:

ExAC

AF:

0.00214

AC:

249

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 02, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely 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	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	PDGFRB: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 26, 2019	This variant is associated with the following publications: (PMID: 30819905, 30761385, 27626691, 26494726) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 01, 2017

- -

Myeloproliferative disorder, chronic, with eosinophilia

Benign:1

Likely 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 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.77

M_CAP

Benign

0.080

MetaRNN

Benign

0.0081

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.26

Polyphen

0.73

Vest4

0.22

MVP

0.63

MPC

0.34

ClinPred

0.0064

GERP RS

0.62

Varity_R

0.070

gMVP

0.79

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