Genetic Variant NM_002609.4:c.3297G>A (chr5-150115787-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002609.4(PDGFRB):c.3297G>A(p.Ala1099Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,609,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

PDGFRB
NM_002609.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.77

Publications

1 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: 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

PDGFRB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 5-150115787-C-T is Benign according to our data. Variant chr5-150115787-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 748062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.77 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000412 (60/1457656) while in subpopulation MID AF = 0.000411 (2/4862). AF 95% confidence interval is 0.000243. There are 0 homozygotes in GnomAdExome4. There are 27 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAdExome4 at 60 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDGFRB	NM_002609.4	MANE Select	c.3297G>A	p.Ala1099Ala	synonymous	Exon 23 of 23	NP_002600.1	P09619-1
PDGFRB	NM_001355016.2		c.3105G>A	p.Ala1035Ala	synonymous	Exon 22 of 22	NP_001341945.1
PDGFRB	NM_001355017.2		c.2814G>A	p.Ala938Ala	synonymous	Exon 23 of 23	NP_001341946.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDGFRB	ENST00000261799.9	TSL:1 MANE Select	c.3297G>A	p.Ala1099Ala	synonymous	Exon 23 of 23	ENSP00000261799.4	P09619-1
PDGFRB	ENST00000520579.5	TSL:1	n.*2611G>A		non_coding_transcript_exon	Exon 23 of 23	ENSP00000430026.1	E5RH16
PDGFRB	ENST00000520579.5	TSL:1	n.*2611G>A		3_prime_UTR	Exon 23 of 23	ENSP00000430026.1	E5RH16

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000689

AC:

AN:

246610

AF XY:

0.0000673

show subpopulations

Gnomad AFR exome

AF:

0.0000630

Gnomad AMR exome

AF:

0.000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.0000412

AC:

AN:

1457656

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

724886

show subpopulations

African (AFR)

AF:

0.0000900

AC:

AN:

33346

American (AMR)

AF:

0.000383

AC:

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39632

South Asian (SAS)

AF:

0.0000583

AC:

AN:

85764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53242

Middle Eastern (MID)

AF:

0.000411

AC:

AN:

4862

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1110262

Other (OTH)

AF:

0.0000166

AC:

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000113

Hom.:

Bravo

AF:

0.0000831

ClinVar

ClinVar submissions

Significance:Likely 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)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.19

(source)

DANN

Benign

0.53

PhyloP100

-3.8

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