rs2307049

Positions:

• chr4-54263987-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000508170.5(PDGFRA):​c.*31G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,502,626 control chromosomes in the GnomAD database, including 19,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2992 hom., cov: 31)
  • Exomes 𝑓: 0.14 (16533 hom.)
• Consequence: PDGFRA ENST00000508170.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.314

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-54263987-G-A is Benign according to our data. Variant chr4-54263987-G-A is described in ClinVar as [Benign]. Clinvar id is 1276038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.628+60G>A		intron_variant		ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000508170.5	c.*31G>A		3_prime_UTR_variant	4/4	1		ENSP00000425648
PDGFRA	ENST00000257290.10	c.628+60G>A		intron_variant		1	NM_006206.6	ENSP00000257290	P1
PDGFRA	ENST00000509490.5	c.628+60G>A		intron_variant, NMD_transcript_variant		1		ENSP00000424218
PDGFRA	ENST00000509092.5	n.446+60G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27392 AN: 151540 Hom.: 2992 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.220 AC: 42546 AN: 193732 Hom.: 5365 AF XY: 0.207 AC XY: 21987 AN XY: 106038

Gnomad AFR exome AF: 0.282

Gnomad AMR exome AF: 0.453

Gnomad ASJ exome AF: 0.0834

Gnomad EAS exome AF: 0.209

Gnomad SAS exome AF: 0.266

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.143 AC: 193429 AN: 1350972 Hom.: 16533 Cov.: 21 AF XY: 0.143 AC XY: 96731 AN XY: 675648

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.0776

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.181 AC: 27423 AN: 151654 Hom.: 2992 Cov.: 31 AF XY: 0.184 AC XY: 13600 AN XY: 74058

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.154

Alfa AF: 0.136 Hom.: 2079

Bravo AF: 0.195

Asia WGS AF: 0.244 AC: 844 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.58

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: rs2307049; hg19: chr4-55130154;