Genetic Variant PDGFRB:p.Thr618Thr (chr5-150124785-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002609.4(PDGFRB):c.1854G>A(p.Thr618Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,609,566 control chromosomes in the GnomAD database, including 1,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 91 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1061 hom. )

Consequence

PDGFRB
NM_002609.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.17

Publications

7 publications found

Variant links:

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

PDGFRB links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 5-150124785-C-T is Benign according to our data. Variant chr5-150124785-C-T is described in ClinVar as Benign. ClinVar VariationId is 473404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0527 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRB	NM_002609.4	MANE Select	c.1854G>A	p.Thr618Thr	synonymous	Exon 13 of 23	NP_002600.1
PDGFRB	NM_001355016.2		c.1662G>A	p.Thr554Thr	synonymous	Exon 12 of 22	NP_001341945.1
PDGFRB	NM_001355017.2		c.1371G>A	p.Thr457Thr	synonymous	Exon 13 of 23	NP_001341946.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRB	ENST00000261799.9	TSL:1 MANE Select	c.1854G>A	p.Thr618Thr	synonymous	Exon 13 of 23	ENSP00000261799.4
PDGFRB	ENST00000520579.5	TSL:1	n.*1168G>A		non_coding_transcript_exon	Exon 13 of 23	ENSP00000430026.1
PDGFRB	ENST00000520579.5	TSL:1	n.*1168G>A		3_prime_UTR	Exon 13 of 23	ENSP00000430026.1

Frequencies

GnomAD3 genomes

AF:

0.0254

AC:

3869

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00585

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0806

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0580

Gnomad FIN

AF:

0.0157

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0326

GnomAD2 exomes

AF:

0.0315

AC:

7833

AN:

248748

AF XY:

0.0349

show subpopulations

Gnomad AFR exome

AF:

0.00540

Gnomad AMR exome

AF:

0.0169

Gnomad ASJ exome

AF:

0.0795

Gnomad EAS exome

AF:

0.000273

Gnomad FIN exome

AF:

0.0160

Gnomad NFE exome

AF:

0.0363

Gnomad OTH exome

AF:

0.0357

GnomAD4 exome

AF:

0.0327

AC:

47729

AN:

1457398

Hom.:

1061

Cov.:

AF XY:

0.0343

AC XY:

24859

AN XY:

725178

show subpopulations

African (AFR)

AF:

0.00569

AC:

190

AN:

33416

American (AMR)

AF:

0.0178

AC:

797

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.0812

AC:

2114

AN:

26044

East Asian (EAS)

AF:

0.000202

AC:

AN:

39690

South Asian (SAS)

AF:

0.0585

AC:

5036

AN:

86060

European-Finnish (FIN)

AF:

0.0185

AC:

970

AN:

52486

Middle Eastern (MID)

AF:

0.0673

AC:

384

AN:

5708

European-Non Finnish (NFE)

AF:

0.0326

AC:

36162

AN:

1109100

Other (OTH)

AF:

0.0343

AC:

2068

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

1908

3816

5725

7633

9541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1298

2596

3894

5192

6490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0254

AC:

3869

AN:

152168

Hom.:

Cov.:

AF XY:

0.0247

AC XY:

1836

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.00583

AC:

242

AN:

41522

American (AMR)

AF:

0.0231

AC:

353

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0806

AC:

280

AN:

3472

East Asian (EAS)

AF:

0.000195

AC:

AN:

5140

South Asian (SAS)

AF:

0.0583

AC:

281

AN:

4824

European-Finnish (FIN)

AF:

0.0157

AC:

167

AN:

10620

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0361

AC:

2452

AN:

67980

Other (OTH)

AF:

0.0323

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

195

389

584

778

973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0349

Hom.:

Bravo

AF:

0.0238

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0402

EpiControl

AF:

0.0427

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

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)

Myeloproliferative disorder, chronic, with eosinophilia (1)

Myofibromatosis, infantile, 1 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.1

(source)

DANN

Benign

0.74

PhyloP100

-4.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over