rs2229562

chr5-150115690-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002609.4(PDGFRB):c.*73A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,407,234 control chromosomes in the GnomAD database, including 121,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12297 hom., cov: 32)
  • Exomes 𝑓: 0.41 (108765 hom.)
• Consequence: PDGFRB NM_002609.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.408

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 5-150115690-T-C is Benign according to our data. Variant chr5-150115690-T-C is described in ClinVar as [Benign]. Clinvar id is 1221159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRB	NM_002609.4	c.*73A>G		3_prime_UTR_variant	23/23	ENST00000261799.9
PDGFRB	NM_001355016.2	c.*73A>G		3_prime_UTR_variant	22/22
PDGFRB	NM_001355017.2	c.*73A>G		3_prime_UTR_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9	c.*73A>G		3_prime_UTR_variant	23/23	1	NM_002609.4	P1
PDGFRB	ENST00000520579.5			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59905 AN: 151914 Hom.: 12274 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.410 AC: 514094 AN: 1255202 Hom.: 108765 Cov.: 18 AF XY: 0.407 AC XY: 250524 AN XY: 615562

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.394 AC: 59971 AN: 152032 Hom.: 12297 Cov.: 32 AF XY: 0.382 AC XY: 28400 AN XY: 74326

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.406

Alfa AF: 0.416 Hom.: 6609

Bravo AF: 0.400

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	5.7
Dann	Benign	0.84

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: rs2229562; hg19: chr5-149495253; COSMIC: COSV53833139; COSMIC: COSV53833139;