rs2291591

Variant names:

• chr4-54281602-C-T
• rs2291591
• NM_006206.6:c.2323+1120C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-54281602-C-T
• chr4-54281602-C-A
• chr4-54281602-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001347827.2(PDGFRA):​c.2345C>T​(p.Thr782Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,352,558 control chromosomes in the GnomAD database, including 5,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (583 hom., cov: 33)
  • Exomes 𝑓: 0.086 (4759 hom.)
• Consequence: PDGFRA NM_001347827.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:3 O:1
• Conservation: PhyloP100: 0.275
• Publications: 13 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 4-54281602-C-T is Benign according to our data. Variant chr4-54281602-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 133374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347827.2. 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.2323+1120C>T		intron	N/A	NP_006197.1	P16234-1
	PDGFRA	NM_001347827.2		c.2345C>T	p.Thr782Met	missense	Exon 17 of 17	NP_001334756.1
	PDGFRA	NM_001347828.2		c.2398+1120C>T		intron	N/A	NP_001334757.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.2323+1120C>T		intron	N/A	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1603+1120C>T		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000507536.1	TSL:1	n.771C>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12757 AN: 152112 Hom.: 582 Cov.: 33

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0725 AC: 9713 AN: 134042 AF XY: 0.0711

Gnomad AFR exome AF: 0.0855

Gnomad AMR exome AF: 0.0543

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.0523

Gnomad FIN exome AF: 0.0743

Gnomad NFE exome AF: 0.0921

Gnomad OTH exome AF: 0.0932

GnomAD4 exome AF: 0.0862 AC: 103495 AN: 1200328 Hom.: 4759 Cov.: 31 AF XY: 0.0844 AC XY: 49542 AN XY: 587084

African (AFR) AF: 0.0850 AC: 2320 AN: 27282

American (AMR) AF: 0.0557 AC: 1674 AN: 30076

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2258 AN: 19956

East Asian (EAS) AF: 0.0726 AC: 1622 AN: 22354

South Asian (SAS) AF: 0.0329 AC: 2523 AN: 76680

European-Finnish (FIN) AF: 0.0761 AC: 998 AN: 13110

Middle Eastern (MID) AF: 0.110 AC: 524 AN: 4762

European-Non Finnish (NFE) AF: 0.0913 AC: 87613 AN: 959316

Other (OTH) AF: 0.0847 AC: 3963 AN: 46792

GnomAD4 genome AF: 0.0839 AC: 12769 AN: 152230 Hom.: 583 Cov.: 33 AF XY: 0.0824 AC XY: 6136 AN XY: 74432

African (AFR) AF: 0.0830 AC: 3445 AN: 41526

American (AMR) AF: 0.0721 AC: 1103 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.0599 AC: 310 AN: 5172

South Asian (SAS) AF: 0.0284 AC: 137 AN: 4826

European-Finnish (FIN) AF: 0.0730 AC: 774 AN: 10596

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0921 AC: 6268 AN: 68020

Other (OTH) AF: 0.102 AC: 216 AN: 2114

Alfa AF: 0.0894 Hom.: 1183

Bravo AF: 0.0850

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer (1)
1	-	-	Myeloproliferative neoplasm, unclassifiable (1)
-	-	1	not specified (2)
-	-	1	PDGFRA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.4
DANN	Benign	0.50
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs2291591; hg19: chr4-55147769; COSMIC: COSV57268339; COSMIC: COSV57268339;