rs246395

Variant names:

• chr5-150120109-T-C
• rs246395
• NM_002609.4:c.2601A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-150120109-T-C
• chr5-150120109-T-A

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.2601A>G​(p.Leu867Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,564,366 control chromosomes in the GnomAD database, including 75,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5805 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69199 hom.)
• Consequence: PDGFRB NM_002609.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.851
• Publications: 38 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 5-150120109-T-C is Benign according to our data. Variant chr5-150120109-T-C is described in ClinVar as Benign. ClinVar VariationId is 258776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.851 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 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.2601A>G	p.Leu867Leu	synonymous	Exon 19 of 23	NP_002600.1	P09619-1
	PDGFRB	NM_001355016.2		c.2409A>G	p.Leu803Leu	synonymous	Exon 18 of 22	NP_001341945.1
	PDGFRB	NM_001355017.2		c.2118A>G	p.Leu706Leu	synonymous	Exon 19 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.2601A>G	p.Leu867Leu	synonymous	Exon 19 of 23	ENSP00000261799.4	P09619-1
	PDGFRB	ENST00000520579.5	TSL:1	n.*1915A>G		non_coding_transcript_exon	Exon 19 of 23	ENSP00000430026.1	E5RH16
	PDGFRB	ENST00000520579.5	TSL:1	n.*1915A>G		3_prime_UTR	Exon 19 of 23	ENSP00000430026.1	E5RH16

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40665 AN: 151950 Hom.: 5791 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.286 AC: 71831 AN: 251184 AF XY: 0.292

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.269

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.135

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.308 AC: 435191 AN: 1412298 Hom.: 69199 Cov.: 26 AF XY: 0.310 AC XY: 218485 AN XY: 705368

African (AFR) AF: 0.165 AC: 5389 AN: 32708

American (AMR) AF: 0.270 AC: 12054 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 8314 AN: 25802

East Asian (EAS) AF: 0.138 AC: 5440 AN: 39496

South Asian (SAS) AF: 0.334 AC: 28497 AN: 85330

European-Finnish (FIN) AF: 0.211 AC: 11273 AN: 53330

Middle Eastern (MID) AF: 0.369 AC: 2089 AN: 5660

European-Non Finnish (NFE) AF: 0.323 AC: 344524 AN: 1066532

Other (OTH) AF: 0.300 AC: 17611 AN: 58778

GnomAD4 genome AF: 0.268 AC: 40713 AN: 152068 Hom.: 5805 Cov.: 32 AF XY: 0.263 AC XY: 19521 AN XY: 74334

African (AFR) AF: 0.174 AC: 7225 AN: 41470

American (AMR) AF: 0.282 AC: 4315 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3470

East Asian (EAS) AF: 0.141 AC: 729 AN: 5166

South Asian (SAS) AF: 0.338 AC: 1632 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2208 AN: 10582

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22514 AN: 67952

Other (OTH) AF: 0.285 AC: 602 AN: 2110

Alfa AF: 0.309 Hom.: 15089

Bravo AF: 0.262

EpiCase AF: 0.329

EpiControl AF: 0.335

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	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	PDGFRB-related disorder (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	-0.56
CADD	Benign	8.4
DANN	Benign	0.56
PhyloP100		0.85
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: rs246395; hg19: chr5-149499672; COSMIC: COSV55800021; COSMIC: COSV55800021;