rs41287112

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002609.4(PDGFRB):c.946G>T(p.Val316Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,408,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V316M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PDGFRB
NM_002609.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.995

Publications

11 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11882514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4 link	c.946G>T	p.Val316Leu	missense_variant	Exon 7 of 23	ENST00000261799.9	NP_002600.1	P09619-1Q59F04
PDGFRB	NM_001355016.2 link	c.754G>T	p.Val252Leu	missense_variant	Exon 6 of 22		NP_001341945.1
PDGFRB	NM_001355017.2 link	c.463G>T	p.Val155Leu	missense_variant	Exon 7 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDGFRB	ENST00000261799.9 link	c.946G>T	p.Val316Leu	missense_variant	Exon 7 of 23	1	NM_002609.4	ENSP00000261799.4	P09619-1
PDGFRB	ENST00000520579.5 link	n.*260G>T		non_coding_transcript_exon_variant	Exon 7 of 23	1		ENSP00000430026.1	E5RH16
PDGFRB	ENST00000520579.5 link	n.*260G>T		3_prime_UTR_variant	Exon 7 of 23	1		ENSP00000430026.1	E5RH16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000596

AC:

AN:

167866

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000103

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1408080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695700

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000311

AC:

AN:

32162

American (AMR)

AF:

0.00

AC:

AN:

36804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25282

East Asian (EAS)

AF:

0.00

AC:

AN:

36802

South Asian (SAS)

AF:

0.00

AC:

AN:

80090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1085130

Other (OTH)

AF:

0.00

AC:

AN:

58296

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.36

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.69

M_CAP

Benign

0.042

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

PhyloP100

0.99

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.4

REVEL

Benign

0.11

Sift

Benign

0.079

Sift4G

Benign

0.13

Polyphen

0.018

Vest4

0.067

MutPred

0.56

Gain of sheet (P = 0.1208);

MVP

0.46

MPC

0.24

ClinPred

0.056

GERP RS

0.62

Varity_R

0.11

gMVP

0.75

Mutation Taster

=88/12

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over