ENST00000257290:c.-104_-103delAG

Variant names:

• chr4-54229321-CAG-C
• rs1799767
• NM_006206.6:c.-104_-103delAG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000257290.10(PDGFRA):​c.-104_-103delAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 398,236 control chromosomes in the GnomAD database, including 10,616 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5016 hom., cov: 23)
  • Exomes 𝑓: 0.21 (5600 hom.)
• Consequence: PDGFRA ENST00000257290.10 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.80
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 4-54229321-CAG-C is Benign according to our data. Variant chr4-54229321-CAG-C is described in ClinVar as Benign. ClinVar VariationId is 348893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000257290.10. 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.-104_-103delAG		5_prime_UTR	Exon 1 of 23	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.-107_-106delAG		5_prime_UTR	Exon 1 of 24	NP_001334757.1
	PDGFRA	NM_001347827.2		c.-104_-103delAG		5_prime_UTR	Exon 1 of 17	NP_001334756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.-104_-103delAG		5_prime_UTR	Exon 1 of 23	ENSP00000257290.5	P16234-1
	PDGFRA	ENST00000508170.5	TSL:1	c.-104_-103delAG		5_prime_UTR	Exon 1 of 4	ENSP00000425648.1	P16234-2
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-45601_1018-45600delAG		intron	N/A	ENSP00000423325.1	A0A0B4J203

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37709 AN: 151816 Hom.: 5010 Cov.: 23

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.207 AC: 50975 AN: 246302 Hom.: 5600 AF XY: 0.205 AC XY: 25563 AN XY: 124808

African (AFR) AF: 0.315 AC: 2265 AN: 7182

American (AMR) AF: 0.362 AC: 2688 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 981 AN: 9240

East Asian (EAS) AF: 0.171 AC: 3913 AN: 22892

South Asian (SAS) AF: 0.257 AC: 780 AN: 3032

European-Finnish (FIN) AF: 0.202 AC: 4207 AN: 20830

Middle Eastern (MID) AF: 0.167 AC: 216 AN: 1294

European-Non Finnish (NFE) AF: 0.205 AC: 32369 AN: 158024

Other (OTH) AF: 0.217 AC: 3556 AN: 16374

GnomAD4 genome AF: 0.249 AC: 37760 AN: 151934 Hom.: 5016 Cov.: 23 AF XY: 0.248 AC XY: 18450 AN XY: 74268

African (AFR) AF: 0.317 AC: 13112 AN: 41358

American (AMR) AF: 0.330 AC: 5038 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1022 AN: 5170

South Asian (SAS) AF: 0.251 AC: 1208 AN: 4820

European-Finnish (FIN) AF: 0.207 AC: 2184 AN: 10574

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14214 AN: 67962

Other (OTH) AF: 0.216 AC: 455 AN: 2110

Alfa AF: 0.228 Hom.: 511

Bravo AF: 0.262

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Gastrointestinal stromal tumor (1)
-	-	1	Idiopathic hypereosinophilic syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
Mutation Taster		=295/5	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: rs1799767; hg19: chr4-55095488;