4-54258772-G-T

Variant names:

• chr4-54258772-G-T
• NM_006206.6:c.4G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006206.6(PDGFRA):​c.4G>T​(p.Gly2Trp) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDGFRA NM_006206.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.22

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38097474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.4G>T	p.Gly2Trp	missense_variant	Exon 2 of 23	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.4G>T	p.Gly2Trp	missense_variant	Exon 2 of 23	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1018-16153G>T		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T;.;T;.;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.52	T;T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.38	T;T;T;T;T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.7	L;L;.;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.16	N;N;N;N;N;N
REVEL	Benign	0.078
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		0.27	B;P;.;.;.;.
Vest4		0.55
MutPred		0.19		Loss of disorder (P = 0.038);Loss of disorder (P = 0.038);.;Loss of disorder (P = 0.038);Loss of disorder (P = 0.038);Loss of disorder (P = 0.038);
MVP		0.64
MPC		1.2
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr4-55124939;