chr5-150115797-G-A

Position:

chr5-150115797-G-A

Variant summary

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

The NM_002609.4(PDGFRB):c.3287C>T(p.Ala1096Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,611,438 control chromosomes in the GnomAD database, including 6 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1096A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 6 hom. )

Consequence

PDGFRB
NM_002609.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.384

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=0.004463464).

BP6

Variant 5-150115797-G-A is Benign according to our data. Variant chr5-150115797-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 707132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150115797-G-A is described in Lovd as [Likely_benign]. Variant chr5-150115797-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00253 (386/152328) while in subpopulation NFE AF= 0.00351 (239/68036). AF 95% confidence interval is 0.00315. There are 0 homozygotes in gnomad4. There are 179 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 386 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDGFRB	NM_002609.4 linkuse as main transcript	c.3287C>T	p.Ala1096Val	missense_variant	23/23	ENST00000261799.9
PDGFRB	NM_001355016.2 linkuse as main transcript	c.3095C>T	p.Ala1032Val	missense_variant	22/22
PDGFRB	NM_001355017.2 linkuse as main transcript	c.2804C>T	p.Ala935Val	missense_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9 linkuse as main transcript	c.3287C>T	p.Ala1096Val	missense_variant	23/23	1	NM_002609.4	P1	P09619-1
PDGFRB	ENST00000520579.5 linkuse as main transcript	c.*2601C>T		3_prime_UTR_variant, NMD_transcript_variant	23/23	1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00442

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00351

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00301

AC:

746

AN:

247568

Hom.:

AF XY:

0.00302

AC XY:

405

AN XY:

134138

show subpopulations

Gnomad AFR exome

AF:

0.000688

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.00471

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00119

Gnomad FIN exome

AF:

0.00471

Gnomad NFE exome

AF:

0.00404

Gnomad OTH exome

AF:

0.00349

GnomAD4 exome

AF:

0.00306

AC:

4471

AN:

1459110

Hom.:

Cov.:

AF XY:

0.00300

AC XY:

2176

AN XY:

725682

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.00238

Gnomad4 ASJ exome

AF:

0.00449

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00508

Gnomad4 NFE exome

AF:

0.00332

Gnomad4 OTH exome

AF:

0.00290

GnomAD4 genome

AF:

0.00253

AC:

386

AN:

152328

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

179

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00442

Gnomad4 NFE

AF:

0.00351

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00314

Hom.:

Bravo

AF:

0.00233

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00306

AC:

371

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00316

EpiControl

AF:

0.00423

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 07, 2021	This variant is associated with the following publications: (PMID: 29084058, 26599395, 24796542) -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Myofibromatosis, infantile, 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

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 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.0

DANN

Benign

0.97

DEOGEN2

Benign

0.25

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.72

M_CAP

Benign

0.084

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.47

REVEL

Benign

0.12

Sift

Uncertain

0.024

Sift4G

Uncertain

0.056

Polyphen

0.18

Vest4

0.036

MVP

0.33

MPC

0.36

ClinPred

0.0038

GERP RS

1.3

Varity_R

0.032

gMVP

0.17

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