rs759729258

chr4-54261320-C-Achr4-54261320-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_006206.6(PDGFRA):c.275C>A(p.Ala92Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A92V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDGFRA NM_006206.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PDGFRA

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRA	NM_006206.6	c.275C>A	p.Ala92Glu	missense_variant	3/23	ENST00000257290.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRA	ENST00000257290.10	c.275C>A	p.Ala92Glu	missense_variant	3/23	1	NM_006206.6	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;T;.;.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.2	M;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	N;N;D;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.063	T;D;D;D;D;D
Sift4G	Benign	0.081	T;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;.
Vest4		0.77
MutPred		0.43		Gain of disorder (P = 0.0498);Gain of disorder (P = 0.0498);.;Gain of disorder (P = 0.0498);Gain of disorder (P = 0.0498);Gain of disorder (P = 0.0498);
MVP		0.71
MPC		1.1
ClinPred		0.94	D
GERP RS		6.0
Varity_R		0.19
gMVP		0.88

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: chr4-55127487;