4-54272451-C-G

Variant names:

• chr4-54272451-C-G
• rs750809787
• NM_006206.6:c.1295C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006206.6(PDGFRA):​c.1295C>G​(p.Thr432Arg) 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. T432M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDGFRA NM_006206.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

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]

PDGFRA Gene-Disease associations (from GenCC):

• gastrointestinal stromal tumor

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• polyps, multiple and recurrent inflammatory fibroid, gastrointestinal

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• isolated cleft palate

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000282278 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006206.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	NM_006206.6	MANE Select	c.1295C>G	p.Thr432Arg	missense	Exon 9 of 23	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.1370C>G	p.Thr457Arg	missense	Exon 10 of 24	NP_001334757.1
	PDGFRA	NM_001347830.2		c.1334C>G	p.Thr445Arg	missense	Exon 9 of 23	NP_001334759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.1295C>G	p.Thr432Arg	missense	Exon 9 of 23	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-2474C>G		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000509092.5	TSL:1	n.1113C>G		non_coding_transcript_exon	Exon 8 of 15

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.013	D
Sift4G	Benign	0.38	T
Polyphen		0.0060	B
Vest4		0.76
MutPred		0.36		Gain of methylation at T432 (P = 0.0287)
MVP		0.84
MPC		0.37
ClinPred		0.17	T
GERP RS		2.4
Varity_R		0.13
gMVP		0.60
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs750809787; hg19: chr4-55138618;