5-150115832-T-C

Variant names:

• chr5-150115832-T-C
• rs246388
• NM_002609.4:c.3252A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002609.4(PDGFRB):​c.3252A>G​(p.Pro1084Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,611,204 control chromosomes in the GnomAD database, including 134,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10631 hom., cov: 33)
  • Exomes 𝑓: 0.40 (123688 hom.)
• Consequence: PDGFRB NM_002609.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -4.13
• Publications: 29 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, Labcorp Genetics (formerly Invitae), Orphanet
• myofibromatosis, infantile, 1

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

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

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-150115832-T-C is Benign according to our data. Variant chr5-150115832-T-C is described in ClinVar as Benign. ClinVar VariationId is 258779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002609.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	NM_002609.4	MANE Select	c.3252A>G	p.Pro1084Pro	synonymous	Exon 23 of 23	NP_002600.1	P09619-1
	PDGFRB	NM_001355016.2		c.3060A>G	p.Pro1020Pro	synonymous	Exon 22 of 22	NP_001341945.1
	PDGFRB	NM_001355017.2		c.2769A>G	p.Pro923Pro	synonymous	Exon 23 of 23	NP_001341946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	ENST00000261799.9	TSL:1 MANE Select	c.3252A>G	p.Pro1084Pro	synonymous	Exon 23 of 23	ENSP00000261799.4	P09619-1
	PDGFRB	ENST00000520579.5	TSL:1	n.*2566A>G		non_coding_transcript_exon	Exon 23 of 23	ENSP00000430026.1	E5RH16
	PDGFRB	ENST00000520579.5	TSL:1	n.*2566A>G		3_prime_UTR	Exon 23 of 23	ENSP00000430026.1	E5RH16

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55566 AN: 152086 Hom.: 10616 Cov.: 33

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.379

GnomAD2 exomes AF: 0.340 AC: 83370 AN: 245412 AF XY: 0.347

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.425

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.404 AC: 589752 AN: 1459000 Hom.: 123688 Cov.: 35 AF XY: 0.403 AC XY: 292118 AN XY: 725644

African (AFR) AF: 0.320 AC: 10666 AN: 33374

American (AMR) AF: 0.257 AC: 11448 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 11037 AN: 26056

East Asian (EAS) AF: 0.112 AC: 4433 AN: 39640

South Asian (SAS) AF: 0.327 AC: 28117 AN: 85866

European-Finnish (FIN) AF: 0.249 AC: 13263 AN: 53328

Middle Eastern (MID) AF: 0.453 AC: 2543 AN: 5612

European-Non Finnish (NFE) AF: 0.436 AC: 484534 AN: 1110382

Other (OTH) AF: 0.394 AC: 23711 AN: 60238

GnomAD4 genome AF: 0.365 AC: 55622 AN: 152204 Hom.: 10631 Cov.: 33 AF XY: 0.354 AC XY: 26307 AN XY: 74412

African (AFR) AF: 0.327 AC: 13583 AN: 41526

American (AMR) AF: 0.339 AC: 5187 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1480 AN: 3470

East Asian (EAS) AF: 0.110 AC: 571 AN: 5172

South Asian (SAS) AF: 0.325 AC: 1571 AN: 4830

European-Finnish (FIN) AF: 0.234 AC: 2478 AN: 10600

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29468 AN: 67984

Other (OTH) AF: 0.378 AC: 798 AN: 2112

Alfa AF: 0.410 Hom.: 6564

Bravo AF: 0.366

Asia WGS AF: 0.216 AC: 752 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Acroosteolysis-keloid-like lesions-premature aging syndrome (1)
-	-	1	Basal ganglia calcification, idiopathic, 4 (1)
-	-	1	Infantile myofibromatosis;C1866182:Acroosteolysis-keloid-like lesions-premature aging syndrome;C3554321:Basal ganglia calcification, idiopathic, 4;C4225270:Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome (1)
-	-	1	Myeloproliferative disorder, chronic, with eosinophilia (1)
-	-	1	Myofibromatosis, infantile, 1 (1)
-	-	1	not provided (1)
-	-	1	Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.19
PhyloP100		-4.1
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: rs246388; hg19: chr5-149495395; COSMIC: COSV53827692; COSMIC: COSV53827692;