chr5-150117796-G-C

Variant names:

• chr5-150117796-G-C
• rs397509382
• NM_002609.4:c.2959C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002609.4(PDGFRB):​c.2959C>G​(p.Arg987Gly) 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. 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. R987Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDGFRB NM_002609.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	NM_002609.4	MANE Select	c.2959C>G	p.Arg987Gly	missense	Exon 22 of 23	NP_002600.1
	PDGFRB	NM_001355016.2		c.2767C>G	p.Arg923Gly	missense	Exon 21 of 22	NP_001341945.1
	PDGFRB	NM_001355017.2		c.2476C>G	p.Arg826Gly	missense	Exon 22 of 23	NP_001341946.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	ENST00000261799.9	TSL:1 MANE Select	c.2959C>G	p.Arg987Gly	missense	Exon 22 of 23	ENSP00000261799.4
	PDGFRB	ENST00000520579.5	TSL:1	n.*2273C>G		non_coding_transcript_exon	Exon 22 of 23	ENSP00000430026.1
	PDGFRB	ENST00000520579.5	TSL:1	n.*2273C>G		3_prime_UTR	Exon 22 of 23	ENSP00000430026.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.43		Loss of solvent accessibility (P = 0.0769)
MVP		0.90
MPC		1.3
ClinPred		1.0	D
GERP RS		2.5
Varity_R		0.39
gMVP		0.64
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs397509382; hg19: chr5-149497359;