rs1553905039

chr4-54278491-A-Cchr4-54278491-A-Gchr4-54278491-A-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.2132A>C(p.Asn711Thr) variant causes a missense change. 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. N711S) 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: 5.00

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=0.23087624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRA	NM_006206.6	c.2132A>C	p.Asn711Thr	missense_variant	15/23	ENST00000257290.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRA	ENST00000257290.10	c.2132A>C	p.Asn711Thr	missense_variant	15/23	1	NM_006206.6	P1
PDGFRA	ENST00000507536.1	n.558A>C		non_coding_transcript_exon_variant	3/5	1
PDGFRA	ENST00000509092.5	n.1950A>C		non_coding_transcript_exon_variant	14/15	1
PDGFRA	ENST00000509490.5	c.2132A>C	p.Asn711Thr	missense_variant, NMD_transcript_variant	15/18	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.040
Eigen_PC	Benign	0.092
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.74	T
MutationTaster	Benign	1.0	N;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.29
Sift	Benign	0.44	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.62	.;P
Vest4		0.40
MutPred		0.52		.;Gain of sheet (P = 0.0085);
MVP		0.50
MPC		0.46
ClinPred		0.67	D
GERP RS		3.6
Varity_R		0.068
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-55144658;