5-150135817-G-T

Variant names:

• chr5-150135817-G-T
• rs17708515
• NM_002609.4:c.102C>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002609.4(PDGFRB):​c.102C>A​(p.Val34Val) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V34V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDGFRB NM_002609.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.989 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.102C>A	p.Val34Val	synonymous_variant	Exon 3 of 23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.-91C>A		5_prime_UTR_variant	Exon 2 of 22		NP_001341945.1
PDGFRB	NM_001355017.2	c.-416C>A		5_prime_UTR_variant	Exon 3 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.102C>A	p.Val34Val	synonymous_variant	Exon 3 of 23	1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5	n.102C>A		non_coding_transcript_exon_variant	Exon 3 of 23	1		ENSP00000430026.1
PDGFRB	ENST00000517957.1	c.102C>A	p.Val34Val	synonymous_variant	Exon 3 of 4	4		ENSP00000430715.1
PDGFRB	ENST00000517488.1	c.-91C>A		5_prime_UTR_variant	Exon 2 of 3	3		ENSP00000429218.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs17708515; hg19: chr5-149515380;