rs1553903757

Variant names:

• chr4-54270725-A-C
• rs1553903757
• NM_006206.6:c.1214A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-54270725-A-C
• chr4-54270725-A-G

Variant summary

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

The NM_001347828.2(PDGFRA):​c.1289A>C​(p.Tyr430Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y430C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDGFRA NM_001347828.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18
• 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: Genomics England PanelApp, Ambry Genetics, G2P
• 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_001347828.2. 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.1214A>C	p.Tyr405Ser	missense	Exon 8 of 23	NP_006197.1
	PDGFRA	NM_001347828.2		c.1289A>C	p.Tyr430Ser	missense	Exon 9 of 24	NP_001334757.1
	PDGFRA	NM_001347830.2		c.1253A>C	p.Tyr418Ser	missense	Exon 8 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.1214A>C	p.Tyr405Ser	missense	Exon 8 of 23	ENSP00000257290.5
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-4200A>C		intron	N/A	ENSP00000423325.1
	PDGFRA	ENST00000509092.5	TSL:1	n.1032A>C		non_coding_transcript_exon	Exon 7 of 15

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Gastrointestinal stromal tumor (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.85
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.29
Sift	Benign	0.14	T
Sift4G	Benign	0.33	T
Polyphen		0.043	B
Vest4		0.67
MutPred		0.61		Gain of disorder (P = 0.0105)
MVP		0.77
MPC		0.50
ClinPred		0.32	T
GERP RS		4.6
Varity_R		0.37
gMVP		0.74
Mutation Taster		=81/19	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: rs1553903757; hg19: chr4-55136892;