rs2302273

Positions:

• chr5-150155692-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002609.4(PDGFRB):​c.-302C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 398,594 control chromosomes in the GnomAD database, including 7,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (2251 hom., cov: 31)
  • Exomes 𝑓: 0.20 (4928 hom.)
• Consequence: PDGFRB NM_002609.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 5-150155692-G-A is Benign according to our data. Variant chr5-150155692-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRB	NM_002609.4	c.-302C>T		5_prime_UTR_variant	1/23	ENST00000261799.9
PDGFRB	NM_001355016.2	c.-448C>T		5_prime_UTR_variant	1/22
PDGFRB	NM_001355017.2	c.-819C>T		5_prime_UTR_variant	1/23
PDGFRB	NR_149150.2	n.154C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9	c.-302C>T		5_prime_UTR_variant	1/23	1	NM_002609.4	P1
PDGFRB	ENST00000520579.5	c.-302C>T		5_prime_UTR_variant, NMD_transcript_variant	1/23	1
PDGFRB	ENST00000517660.1	n.169C>T		non_coding_transcript_exon_variant	1/2	3
PDGFRB	ENST00000523456.1	n.181C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23284 AN: 152088 Hom.: 2251 Cov.: 31

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.195 AC: 48132 AN: 246390 Hom.: 4928 Cov.: 0 AF XY: 0.198 AC XY: 24691 AN XY: 124886

Gnomad4 AFR exome AF: 0.0503

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.153 AC: 23285 AN: 152204 Hom.: 2251 Cov.: 31 AF XY: 0.150 AC XY: 11164 AN XY: 74420

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.200

Alfa AF: 0.208 Hom.: 7056

Bravo AF: 0.152

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.90

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: rs2302273; hg19: chr5-149535255;