5-150117665-G-A

Variant names:

• chr5-150117665-G-A
• rs2228440
• NM_002609.4:c.3090C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002609.4(PDGFRB):​c.3090C>T​(p.Pro1030Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 1,613,136 control chromosomes in the GnomAD database, including 8,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (628 hom., cov: 31)
  • Exomes 𝑓: 0.098 (7744 hom.)
• Consequence: PDGFRB NM_002609.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -4.01
• Publications: 18 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• basal ganglia calcification, idiopathic, 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 5-150117665-G-A is Benign according to our data. Variant chr5-150117665-G-A is described in ClinVar as Benign. ClinVar VariationId is 258777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 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.3090C>T	p.Pro1030Pro	synonymous	Exon 22 of 23	NP_002600.1	P09619-1
	PDGFRB	NM_001355016.2		c.2898C>T	p.Pro966Pro	synonymous	Exon 21 of 22	NP_001341945.1
	PDGFRB	NM_001355017.2		c.2607C>T	p.Pro869Pro	synonymous	Exon 22 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.3090C>T	p.Pro1030Pro	synonymous	Exon 22 of 23	ENSP00000261799.4	P09619-1
	PDGFRB	ENST00000520579.5	TSL:1	n.*2404C>T		non_coding_transcript_exon	Exon 22 of 23	ENSP00000430026.1	E5RH16
	PDGFRB	ENST00000520579.5	TSL:1	n.*2404C>T		3_prime_UTR	Exon 22 of 23	ENSP00000430026.1	E5RH16

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13399 AN: 151928 Hom.: 629 Cov.: 31

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0864

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0858

GnomAD2 exomes AF: 0.0763 AC: 19165 AN: 251228 AF XY: 0.0771

Gnomad AFR exome AF: 0.0853

Gnomad AMR exome AF: 0.0587

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0550

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.0821

GnomAD4 exome AF: 0.0981 AC: 143318 AN: 1461090 Hom.: 7744 Cov.: 32 AF XY: 0.0966 AC XY: 70209 AN XY: 726890

African (AFR) AF: 0.0838 AC: 2803 AN: 33468

American (AMR) AF: 0.0609 AC: 2723 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2877 AN: 26134

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39694

South Asian (SAS) AF: 0.0387 AC: 3336 AN: 86240

European-Finnish (FIN) AF: 0.0600 AC: 3207 AN: 53410

Middle Eastern (MID) AF: 0.0826 AC: 476 AN: 5764

European-Non Finnish (NFE) AF: 0.110 AC: 121992 AN: 1111298

Other (OTH) AF: 0.0976 AC: 5895 AN: 60370

GnomAD4 genome AF: 0.0881 AC: 13398 AN: 152046 Hom.: 628 Cov.: 31 AF XY: 0.0840 AC XY: 6240 AN XY: 74316

African (AFR) AF: 0.0850 AC: 3523 AN: 41466

American (AMR) AF: 0.0863 AC: 1318 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.0417 AC: 201 AN: 4820

European-Finnish (FIN) AF: 0.0462 AC: 488 AN: 10574

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7172 AN: 67970

Other (OTH) AF: 0.0849 AC: 179 AN: 2108

Alfa AF: 0.0999 Hom.: 807

Bravo AF: 0.0913

Asia WGS AF: 0.0250 AC: 87 AN: 3478

EpiCase AF: 0.107

EpiControl AF: 0.108

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	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	-0.63
CADD	Benign	0.78
DANN	Benign	0.81
PhyloP100		-4.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2228440; hg19: chr5-149497228;