4-54274941-G-C

Variant names:

• chr4-54274941-G-C
• NM_006206.6:c.1754G>C

Variant summary

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

The NM_006206.6(PDGFRA):​c.1754G>C​(p.Arg585Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDGFRA NM_006206.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

Genes affected

PDGFRA (HGNC:8803): (platelet derived growth factor receptor alpha) This gene encodes 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 or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]

ENSG00000282278 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.1754G>C	p.Arg585Thr	missense_variant	Exon 12 of 23	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.1754G>C	p.Arg585Thr	missense_variant	Exon 12 of 23	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1034G>C	p.Arg345Thr	missense_variant	Exon 13 of 24	2		ENSP00000423325.1
PDGFRA	ENST00000509092.5	n.1572G>C		non_coding_transcript_exon_variant	Exon 11 of 15	1
PDGFRA	ENST00000509490.5	n.1754G>C		non_coding_transcript_exon_variant	Exon 12 of 18	1		ENSP00000424218.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	25
DANN	Benign	0.90
DEOGEN2	Benign	0.14	.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Uncertain	0.76	D
MutationAssessor	Benign	1.4	.;L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.010	N;N
REVEL	Uncertain	0.60
Sift	Benign	0.32	T;T
Sift4G	Benign	0.15	T;T
Polyphen		1.0	.;D
Vest4		0.55
MutPred		0.50		.;Loss of solvent accessibility (P = 0.0435);
MVP		0.91
MPC		1.3
ClinPred		0.62	D
GERP RS		6.0
Varity_R		0.73
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-55141108;