rs201503614

chr4-54274887-C-Achr4-54274887-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.1700C>A(p.Pro567Gln) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P567L) 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: 5.78

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.1700C>A	p.Pro567Gln	missense_variant	12/23	ENST00000257290.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRA	ENST00000257290.10	c.1700C>A	p.Pro567Gln	missense_variant	12/23	1	NM_006206.6	P1
PDGFRA	ENST00000509092.5	n.1518C>A		non_coding_transcript_exon_variant	11/15	1
PDGFRA	ENST00000509490.5	c.1700C>A	p.Pro567Gln	missense_variant, NMD_transcript_variant	12/18	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
Cadd	Pathogenic	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.56
Sift	Benign	0.17	T
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.35		Loss of sheet (P = 0.0228);
MVP		0.86
MPC		1.0
ClinPred		0.79	D
GERP RS		5.8
Varity_R		0.40
gMVP		0.85

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

LitVar

Other links and lift over

dbSNP: rs201503614; hg19: chr4-55141054;