rs1554107047

Positions:

• chr5-150115843-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002609.4(PDGFRB):​c.3241G>A​(p.Glu1081Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDGFRB NM_002609.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.70

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18371594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.3241G>A	p.Glu1081Lys	missense_variant	23/23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.3049G>A	p.Glu1017Lys	missense_variant	22/22		NP_001341945.1
PDGFRB	NM_001355017.2	c.2758G>A	p.Glu920Lys	missense_variant	23/23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.3241G>A	p.Glu1081Lys	missense_variant	23/23	1	NM_002609.4	ENSP00000261799	P1
PDGFRB	ENST00000520579.5	c.*2555G>A		3_prime_UTR_variant, NMD_transcript_variant	23/23	1		ENSP00000430026

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Basal ganglia calcification, idiopathic, 4 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2016

This variant was classified as: Uncertain significance. -

Parkinsonian disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.21
Sift	Benign	0.050	D
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.15		Gain of ubiquitination at E1081 (P = 7e-04);
MVP		0.75
MPC		0.45
ClinPred		0.13	T
GERP RS		2.9
Varity_R		0.064
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs1554107047; hg19: chr5-149495406;