rs2229562

Variant names:

• chr5-150115690-T-C
• rs2229562
• NM_002609.4:c.*73A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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 -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 VariationId 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 rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.*73A>G		3_prime_UTR_variant	Exon 23 of 23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.*73A>G		3_prime_UTR_variant	Exon 22 of 22		NP_001341945.1
PDGFRB	NM_001355017.2	c.*73A>G		3_prime_UTR_variant	Exon 23 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.*73A>G		3_prime_UTR_variant	Exon 23 of 23	1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5	n.*2708A>G		downstream_gene_variant		1		ENSP00000430026.1

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

African (AFR) AF: 0.415 AC: 11329 AN: 27296

American (AMR) AF: 0.259 AC: 6715 AN: 25898

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 8538 AN: 18716

East Asian (EAS) AF: 0.109 AC: 3980 AN: 36428

South Asian (SAS) AF: 0.320 AC: 20261 AN: 63326

European-Finnish (FIN) AF: 0.248 AC: 10005 AN: 40274

Middle Eastern (MID) AF: 0.451 AC: 1585 AN: 3512

European-Non Finnish (NFE) AF: 0.436 AC: 430686 AN: 987544

Other (OTH) AF: 0.402 AC: 20995 AN: 52208

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

African (AFR) AF: 0.423 AC: 17527 AN: 41442

American (AMR) AF: 0.354 AC: 5406 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1604 AN: 3468

East Asian (EAS) AF: 0.110 AC: 569 AN: 5154

South Asian (SAS) AF: 0.326 AC: 1569 AN: 4814

European-Finnish (FIN) AF: 0.234 AC: 2485 AN: 10604

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29467 AN: 67952

Other (OTH) AF: 0.406 AC: 856 AN: 2110

Alfa AF: 0.417 Hom.: 9056

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

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.7
DANN	Benign	0.84
PhyloP100		-0.41
Mutation Taster		=100/0	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: rs2229562; hg19: chr5-149495253; COSMIC: COSV53833139; COSMIC: COSV53833139;