4-54229515-G-GA

Position:

• chr4-54229515-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006206.6(PDGFRA):​c.-13+111dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 311,106 control chromosomes in the GnomAD database, including 5,482 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5046 hom., cov: 21)
  • Exomes 𝑓: 0.27 (436 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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 -10 ACMG points.

• BP6: Variant 4-54229515-G-GA is Benign according to our data. Variant chr4-54229515-G-GA is described in ClinVar as [Benign]. Clinvar id is 1257913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRA	NM_006206.6	c.-13+111dup		intron_variant		ENST00000257290.10
PDGFRA	NM_001347827.2	c.-13+111dup		intron_variant
PDGFRA	NM_001347828.2	c.-16+111dup		intron_variant
PDGFRA	XM_006714041.4	c.-16+111dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRA	ENST00000257290.10	c.-13+111dup		intron_variant		1	NM_006206.6	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 37271 AN: 142140 Hom.: 5042 Cov.: 21

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.268 AC: 45251 AN: 168920 Hom.: 436 AF XY: 0.266 AC XY: 22817 AN XY: 85728

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.262 AC: 37306 AN: 142186 Hom.: 5046 Cov.: 21 AF XY: 0.263 AC XY: 18106 AN XY: 68850

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.232

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2019

- -

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: rs565335773; hg19: chr4-55095682;