rs246395

Variant names:

• chr5-150120109-T-A
• rs246395
• NM_002609.4:c.2601A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-150120109-T-A
• chr5-150120109-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002609.4(PDGFRB):​c.2601A>T​(p.Leu867Phe) 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 pathogenic 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. L867L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDGFRB NM_002609.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.2601A>T	p.Leu867Phe	missense_variant	Exon 19 of 23	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.2409A>T	p.Leu803Phe	missense_variant	Exon 18 of 22		NP_001341945.1
PDGFRB	NM_001355017.2	c.2118A>T	p.Leu706Phe	missense_variant	Exon 19 of 23		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.2601A>T	p.Leu867Phe	missense_variant	Exon 19 of 23	1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5	n.*1915A>T		non_coding_transcript_exon_variant	Exon 19 of 23	1		ENSP00000430026.1
PDGFRB	ENST00000520579.5	n.*1915A>T		3_prime_UTR_variant	Exon 19 of 23	1		ENSP00000430026.1
PDGFRB	ENST00000519575.5	n.515A>T		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1418486 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 708198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.66		Loss of catalytic residue at L867 (P = 0.073);
MVP		0.90
MPC		1.2
ClinPred		0.90	D
GERP RS		2.7
Varity_R		0.21
gMVP		0.84

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: rs246395; hg19: chr5-149499672;