5-150133957-C-T

Position:

• chr5-150133957-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PM2 PP3_Strong BP6_Moderate

The NM_002609.4(PDGFRB):​c.683G>A​(p.Gly228Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDGFRB NM_002609.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.43

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974
• BP6: Variant 5-150133957-C-T is Benign according to our data. Variant chr5-150133957-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 191201.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.683G>A	p.Gly228Asp	missense_variant	5/23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.491G>A	p.Gly164Asp	missense_variant	4/22		NP_001341945.1
PDGFRB	NM_001355017.2	c.200G>A	p.Gly67Asp	missense_variant	5/23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.683G>A	p.Gly228Asp	missense_variant	5/23	1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5	n.717G>A		non_coding_transcript_exon_variant	5/23	1		ENSP00000430026.1
PDGFRB	ENST00000522466.1	n.154G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Sep 28, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.024	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.92		Gain of solvent accessibility (P = 0.008);
MVP		0.65
MPC		0.98
ClinPred		0.85	D
GERP RS		5.9
Varity_R		0.84
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs374239531; hg19: chr5-149513520; COSMIC: COSV55809278; COSMIC: COSV55809278;