rs199902153

chr4-54277492-C-Gchr4-54277492-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_006206.6(PDGFRA):c.1891C>G(p.Pro631Ala) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. P631S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDGFRA NM_006206.6 missense, splice_region
• Scores: Splicing: ADA: 0.8119
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96

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 2 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=0.3103339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRA	NM_006206.6	c.1891C>G	p.Pro631Ala	missense_variant, splice_region_variant	13/23	ENST00000257290.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRA	ENST00000257290.10	c.1891C>G	p.Pro631Ala	missense_variant, splice_region_variant	13/23	1	NM_006206.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Pathogenic	27
Dann	Uncertain	0.99
Eigen	Benign	-0.11
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.56	T
MutationTaster	Benign	0.98	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.40
Sift	Benign	0.17	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.62	.;P
Vest4		0.42
MutPred		0.41		.;Loss of sheet (P = 0.0126);
MVP		0.59
MPC		0.58
ClinPred		0.44	T
GERP RS		5.6
Varity_R		0.22
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.81
dbscSNV1_RF	Benign	0.52
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: chr4-55143659;