rs778327861

chr4-54288835-C-Gchr4-54288835-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_006206.6(PDGFRA):c.2711C>G(p.Thr904Ser) 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. 13/21 in silico tools predict a benign 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. T904A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDGFRA NM_006206.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PDGFRA
• BP4: Computational evidence support a benign effect (MetaRNN=0.18835422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRA	NM_006206.6	c.2711C>G	p.Thr904Ser	missense_variant	20/23	ENST00000257290.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRA	ENST00000257290.10	c.2711C>G	p.Thr904Ser	missense_variant	20/23	1	NM_006206.6	P1

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	0.057
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	21
Dann	Uncertain	0.98
Eigen	Benign	-0.063
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.59	T
MutationTaster	Benign	1.0	N;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.50	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.36	T;T
Sift4G	Benign	0.72	T;T
Polyphen		0.0040	.;B
Vest4		0.22
MutPred		0.45		.;Loss of phosphorylation at T904 (P = 0.039);
MVP		0.38
MPC		1.4
ClinPred		0.27	T
GERP RS		6.1
Varity_R		0.28
gMVP		0.15

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: chr4-55155002;