rs41287108

chr5-150120951-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BS1 BS2

The NM_002609.4(PDGFRB):c.2523G>A(p.Lys841=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,613,974 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (27 hom.)
• Consequence: PDGFRB NM_002609.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.77

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 5-150120951-C-T is Benign according to our data. Variant chr5-150120951-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 286389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150120951-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=2.77 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00243 (370/152278) while in subpopulation AMR AF= 0.00412 (63/15308). AF 95% confidence interval is 0.0033. There are 2 homozygotes in gnomad4. There are 179 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 369 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRB	NM_002609.4	c.2523G>A	p.Lys841=	synonymous_variant	18/23	ENST00000261799.9
PDGFRB	NM_001355016.2	c.2331G>A	p.Lys777=	synonymous_variant	17/22
PDGFRB	NM_001355017.2	c.2040G>A	p.Lys680=	synonymous_variant	18/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9	c.2523G>A	p.Lys841=	synonymous_variant	18/23	1	NM_002609.4	P1
PDGFRB	ENST00000520579.5	c.*1837G>A		3_prime_UTR_variant, NMD_transcript_variant	18/23	1
PDGFRB	ENST00000519575.5	n.437G>A		non_coding_transcript_exon_variant	4/6	3
PDGFRB	ENST00000521723.1	n.376G>A		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 369 AN: 152160 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00359

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00309 AC: 777 AN: 251468 Hom.: 4 AF XY: 0.00349 AC XY: 475 AN XY: 135918

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00615

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00252

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00446

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00353 AC: 5164 AN: 1461696 Hom.: 27 Cov.: 32 AF XY: 0.00369 AC XY: 2683 AN XY: 727164

Gnomad4 AFR exome AF: 0.000777

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.00601

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00330

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.00384

Gnomad4 OTH exome AF: 0.00387

GnomAD4 genome AF: 0.00243 AC: 370 AN: 152278 Hom.: 2 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74456

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00360

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00382 Hom.: 0

Bravo AF: 0.00272

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00654

EpiControl AF: 0.00723

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 28, 2021	This variant is associated with the following publications: (PMID: 27535533) -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	PDGFRB: BP4, BS2 -
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	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 08, 2016

- -

PDGFRB-related condition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 12, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Invitae

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
Cadd	Benign	10
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs41287108; hg19: chr5-149500514;