4-54229560-A-AT

Position:

• chr4-54229560-A-AT

Variant summary

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

The NM_006206.6(PDGFRA):​c.-13+156dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 315,112 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0087 (12 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.284

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 4-54229560-A-AT is Benign according to our data. Variant chr4-54229560-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 1195004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.-13+156dup		intron_variant		ENST00000257290.10	NP_006197.1
PDGFRA	NM_001347827.2	c.-13+156dup		intron_variant			NP_001334756.1
PDGFRA	NM_001347828.2	c.-16+156dup		intron_variant			NP_001334757.1
PDGFRA	XM_006714041.4	c.-16+156dup		intron_variant			XP_006714104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.-13+156dup		intron_variant		1	NM_006206.6	ENSP00000257290	P1

Frequencies

GnomAD3 genomes AF: 0.00869 AC: 1292 AN: 148682 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00293

Gnomad SAS AF: 0.000848

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.00891

GnomAD4 exome AF: 0.0377 AC: 6277 AN: 166368 Hom.: 1 AF XY: 0.0370 AC XY: 3114 AN XY: 84252

Gnomad4 AFR exome AF: 0.0617

Gnomad4 AMR exome AF: 0.0418

Gnomad4 ASJ exome AF: 0.0377

Gnomad4 EAS exome AF: 0.0350

Gnomad4 SAS exome AF: 0.0334

Gnomad4 FIN exome AF: 0.0321

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0406

GnomAD4 genome AF: 0.00867 AC: 1290 AN: 148744 Hom.: 12 Cov.: 31 AF XY: 0.00804 AC XY: 583 AN XY: 72482

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00274

Gnomad4 SAS AF: 0.000851

Gnomad4 FIN AF: 0.00103

Gnomad4 NFE AF: 0.000911

Gnomad4 OTH AF: 0.00882

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 30, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs920838716; hg19: chr4-55095727;