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.102C>T(p.Val34Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00742 in 1,579,558 control chromosomes in the GnomAD database, including 401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 49 hom., cov: 33)

Exomes 𝑓: 0.0070 ( 352 hom. )

Consequence

PDGFRB
NM_002609.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.989

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:

Genome browser will be placed here

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=-0.38).

BP6

Variant 5-150135817-G-A is Benign according to our data. Variant chr5-150135817-G-A is described in ClinVar as Benign. ClinVar VariationId is 473399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.989 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0537 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.102C>T	p.Val34Val	synonymous	Exon 3 of 23	NP_002600.1
PDGFRB	NM_001355016.2		c.-91C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 22	NP_001341945.1
PDGFRB	NM_001355017.2		c.-416C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 23	NP_001341946.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRB	ENST00000261799.9	TSL:1 MANE Select	c.102C>T	p.Val34Val	synonymous	Exon 3 of 23	ENSP00000261799.4
PDGFRB	ENST00000520579.5	TSL:1	n.102C>T		non_coding_transcript_exon	Exon 3 of 23	ENSP00000430026.1
PDGFRB	ENST00000517488.1	TSL:3	c.-91C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000429218.1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1656

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00956

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0366

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0360

Gnomad SAS

AF:

0.0599

Gnomad FIN

AF:

0.0141

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00767

GnomAD2 exomes

AF:

0.0212

AC:

4649

AN:

219058

AF XY:

0.0198

show subpopulations

Gnomad AFR exome

AF:

0.00875

Gnomad AMR exome

AF:

0.0776

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0306

Gnomad FIN exome

AF:

0.0152

Gnomad NFE exome

AF:

0.000901

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.00703

AC:

10030

AN:

1427270

Hom.:

352

Cov.:

AF XY:

0.00793

AC XY:

5606

AN XY:

706806

show subpopulations

African (AFR)

AF:

0.00938

AC:

304

AN:

32400

American (AMR)

AF:

0.0723

AC:

2898

AN:

40086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23626

East Asian (EAS)

AF:

0.0245

AC:

961

AN:

39304

South Asian (SAS)

AF:

0.0497

AC:

3964

AN:

79762

European-Finnish (FIN)

AF:

0.0154

AC:

803

AN:

52128

Middle Eastern (MID)

AF:

0.00305

AC:

AN:

5576

European-Non Finnish (NFE)

AF:

0.000381

AC:

417

AN:

1095476

Other (OTH)

AF:

0.0113

AC:

666

AN:

58912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

411

822

1232

1643

2054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<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:

0.0111

AC:

1683

AN:

152288

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

934

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00991

AC:

412

AN:

41558

American (AMR)

AF:

0.0371

AC:

567

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0361

AC:

187

AN:

5182

South Asian (SAS)

AF:

0.0593

AC:

286

AN:

4820

European-Finnish (FIN)

AF:

0.0141

AC:

150

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68020

Other (OTH)

AF:

0.0109

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

164

246

328

410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00386

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

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)

PDGFRB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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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rs17708515

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over