rs41287108

Variant names:

• chr5-150120951-C-T
• rs41287108
• NM_002609.4:c.2523G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BS1 BS2

The NM_002609.4(PDGFRB):​c.2523G>A​(p.Lys841Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,613,974 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (27 hom.)
• Consequence: PDGFRB NM_002609.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 2.77
• Publications: 3 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 5-150120951-C-T is Benign according to our data. Variant chr5-150120951-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 286389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.77 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00243 (370/152278) while in subpopulation AMR AF = 0.00412 (63/15308). AF 95% confidence interval is 0.0033. There are 2 homozygotes in GnomAd4. There are 179 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 370 AD gene.

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.2523G>A	p.Lys841Lys	synonymous	Exon 18 of 23	NP_002600.1	P09619-1
	PDGFRB	NM_001355016.2		c.2331G>A	p.Lys777Lys	synonymous	Exon 17 of 22	NP_001341945.1
	PDGFRB	NM_001355017.2		c.2040G>A	p.Lys680Lys	synonymous	Exon 18 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.2523G>A	p.Lys841Lys	synonymous	Exon 18 of 23	ENSP00000261799.4	P09619-1
	PDGFRB	ENST00000520579.5	TSL:1	n.*1837G>A		non_coding_transcript_exon	Exon 18 of 23	ENSP00000430026.1	E5RH16
	PDGFRB	ENST00000520579.5	TSL:1	n.*1837G>A		3_prime_UTR	Exon 18 of 23	ENSP00000430026.1	E5RH16

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 369 AN: 152160 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00359

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00309 AC: 777 AN: 251468 AF XY: 0.00349

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00615

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00446

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00353 AC: 5164 AN: 1461696 Hom.: 27 Cov.: 32 AF XY: 0.00369 AC XY: 2683 AN XY: 727164

African (AFR) AF: 0.000777 AC: 26 AN: 33474

American (AMR) AF: 0.00264 AC: 118 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00601 AC: 157 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00330 AC: 285 AN: 86252

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53420

Middle Eastern (MID) AF: 0.0101 AC: 58 AN: 5768

European-Non Finnish (NFE) AF: 0.00384 AC: 4272 AN: 1111830

Other (OTH) AF: 0.00387 AC: 234 AN: 60392

GnomAD4 genome AF: 0.00243 AC: 370 AN: 152278 Hom.: 2 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74456

African (AFR) AF: 0.000578 AC: 24 AN: 41558

American (AMR) AF: 0.00412 AC: 63 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4812

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00360 AC: 245 AN: 68018

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00384 Hom.: 0

Bravo AF: 0.00272

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00654

EpiControl AF: 0.00723

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	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 specified (1)
-	-	1	PDGFRB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		2.8
Mutation Taster		=77/23	polymorphism

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: rs41287108; hg19: chr5-149500514;