rs2302273

Variant names:

• chr5-150155692-G-A
• rs2302273
• ENST00000520579.5:n.-302C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520579.5(PDGFRB):​n.-302C>T variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2251 hom., cov: 31)
  • Exomes 𝑓: 0.20 (4928 hom.)
• Consequence: PDGFRB ENST00000520579.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• acroosteolysis-keloid-like lesions-premature aging syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• myofibromatosis, infantile, 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• basal ganglia calcification, idiopathic, 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile myofibromatosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary progressive mucinous histiocytosis

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• 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 rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.-302C>T		5_prime_UTR_variant	Exon 1 of 23	ENST00000261799.9	NP_002600.1
PDGFRB	NR_149150.2	n.154C>T		non_coding_transcript_exon_variant	Exon 1 of 2
PDGFRB	NM_001355016.2	c.-448C>T		5_prime_UTR_variant	Exon 1 of 22		NP_001341945.1
PDGFRB	NM_001355017.2	c.-819C>T		5_prime_UTR_variant	Exon 1 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.-302C>T		5_prime_UTR_variant	Exon 1 of 23	1	NM_002609.4	ENSP00000261799.4

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

African (AFR) AF: 0.0503 AC: 361 AN: 7182

American (AMR) AF: 0.174 AC: 1290 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 2916 AN: 9240

East Asian (EAS) AF: 0.135 AC: 3094 AN: 22896

South Asian (SAS) AF: 0.131 AC: 397 AN: 3036

European-Finnish (FIN) AF: 0.156 AC: 3247 AN: 20820

Middle Eastern (MID) AF: 0.283 AC: 367 AN: 1298

European-Non Finnish (NFE) AF: 0.210 AC: 33144 AN: 158110

Other (OTH) AF: 0.202 AC: 3316 AN: 16376

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

African (AFR) AF: 0.0442 AC: 1835 AN: 41542

American (AMR) AF: 0.183 AC: 2797 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3468

East Asian (EAS) AF: 0.130 AC: 670 AN: 5166

South Asian (SAS) AF: 0.133 AC: 641 AN: 4828

European-Finnish (FIN) AF: 0.142 AC: 1508 AN: 10608

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14059 AN: 67982

Other (OTH) AF: 0.200 AC: 423 AN: 2112

Alfa AF: 0.196 Hom.: 13388

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
PhyloP100		0.40
PromoterAI		-0.14	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2302273; hg19: chr5-149535255;