rs55634318

Positions:

• chr22-39231625-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000331163.11(PDGFB):​c.453C>G​(p.Val151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,562,296 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (51 hom., cov: 32)
  • Exomes 𝑓: 0.013 (125 hom.)
• Consequence: PDGFB ENST00000331163.11 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.632

Genes affected

PDGFB (HGNC:8800): (platelet derived growth factor subunit B) This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit B, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit A. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where this gene and that for collagen type 1, alpha 1 are located, are associated with dermatofibrosarcoma protuberans, a rare skin tumor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-39231625-G-C is Benign according to our data. Variant chr22-39231625-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1188397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-39231625-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.632 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0197 (3008/152310) while in subpopulation AFR AF= 0.0385 (1601/41570). AF 95% confidence interval is 0.0369. There are 51 homozygotes in gnomad4. There are 1455 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3008 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.453C>G	p.Val151=	synonymous_variant	4/7	ENST00000331163.11	NP_002599.1
PDGFB	NM_033016.3	c.408C>G	p.Val136=	synonymous_variant	4/7		NP_148937.1
PDGFB	XM_047441393.1	c.360C>G	p.Val120=	synonymous_variant	4/7		XP_047297349.1
PDGFB	XM_047441394.1	c.360C>G	p.Val120=	synonymous_variant	4/7		XP_047297350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.453C>G	p.Val151=	synonymous_variant	4/7	1	NM_002608.4	ENSP00000330382	P1
PDGFB	ENST00000381551.8	c.408C>G	p.Val136=	synonymous_variant	4/7	5		ENSP00000370963
PDGFB	ENST00000455790.5	c.360C>G	p.Val120=	synonymous_variant	4/5	4		ENSP00000402306
PDGFB	ENST00000440375.1	c.360C>G	p.Val120=	synonymous_variant	4/5	4		ENSP00000405780

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2978 AN: 152192 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0117 AC: 2011 AN: 171928 Hom.: 15 AF XY: 0.0114 AC XY: 1053 AN XY: 92268

Gnomad AFR exome AF: 0.0352

Gnomad AMR exome AF: 0.00935

Gnomad ASJ exome AF: 0.00712

Gnomad EAS exome AF: 0.000227

Gnomad SAS exome AF: 0.0146

Gnomad FIN exome AF: 0.00448

Gnomad NFE exome AF: 0.0123

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0130 AC: 18377 AN: 1409986 Hom.: 125 Cov.: 31 AF XY: 0.0130 AC XY: 9050 AN XY: 697104

Gnomad4 AFR exome AF: 0.0378

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00771

Gnomad4 EAS exome AF: 0.0000808

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.00476

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0148

GnomAD4 genome AF: 0.0197 AC: 3008 AN: 152310 Hom.: 51 Cov.: 32 AF XY: 0.0195 AC XY: 1455 AN XY: 74486

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0147 Hom.: 6

Bravo AF: 0.0212

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

PDGFB-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55634318; hg19: chr22-39627630;