4-54229321-CAG-C

Position:

• chr4-54229321-CAG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006206.6(PDGFRA):​c.-104_-103del 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 NM_006206.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.80

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.-104_-103del		5_prime_UTR_variant	1/23	ENST00000257290.10	NP_006197.1
PDGFRA	NM_001347827.2	c.-104_-103del		5_prime_UTR_variant	1/17		NP_001334756.1
PDGFRA	NM_001347828.2	c.-107_-106del		5_prime_UTR_variant	1/24		NP_001334757.1
PDGFRA	XM_006714041.4	c.-107_-106del		5_prime_UTR_variant	1/18		XP_006714104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.-104_-103del		5_prime_UTR_variant	1/23	1	NM_006206.6	ENSP00000257290	P1

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

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.217

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

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.216

Alfa AF: 0.228 Hom.: 511

Bravo AF: 0.262

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Idiopathic hypereosinophilic syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Gastrointestinal stromal tumor Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1799767; hg19: chr4-55095488;