Variant rs2291591 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006206.6(PDGFRA):c.2323+1120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,352,558 control chromosomes in the GnomAD database, including 5,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.084 ( 583 hom., cov: 33)

Exomes 𝑓: 0.086 ( 4759 hom. )

Consequence

PDGFRA
NM_006206.6 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1B:2O:1

Conservation

PhyloP100: 0.275

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRA	NM_006206.6 linkuse as main transcript	c.2323+1120C>T		intron_variant		ENST00000257290.10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRA	ENST00000257290.10 linkuse as main transcript	c.2323+1120C>T	intron_variant		1	NM_006206.6	P1	P16234-1
PDGFRA	ENST00000507536.1 linkuse as main transcript	n.771C>T	non_coding_transcript_exon_variant	5/5	1
PDGFRA	ENST00000509490.5 linkuse as main transcript	c.*266C>T	3_prime_UTR_variant, NMD_transcript_variant	18/18	1			P16234-3

Frequencies

GnomAD3 genomes

AF:

0.0839

AC:

12757

AN:

152112

Hom.:

582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0829

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.0594

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.0730

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0922

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.0725

AC:

9713

AN:

134042

Hom.:

411

AF XY:

0.0711

AC XY:

5192

AN XY:

72976

show subpopulations

Gnomad AFR exome

AF:

0.0855

Gnomad AMR exome

AF:

0.0543

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.0523

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.0743

Gnomad NFE exome

AF:

0.0921

Gnomad OTH exome

AF:

0.0932

GnomAD4 exome

AF:

0.0862

AC:

103495

AN:

1200328

Hom.:

4759

Cov.:

AF XY:

0.0844

AC XY:

49542

AN XY:

587084

show subpopulations

Gnomad4 AFR exome

AF:

0.0850

Gnomad4 AMR exome

AF:

0.0557

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.0726

Gnomad4 SAS exome

AF:

0.0329

Gnomad4 FIN exome

AF:

0.0761

Gnomad4 NFE exome

AF:

0.0913

Gnomad4 OTH exome

AF:

0.0847

GnomAD4 genome

AF:

0.0839

AC:

12769

AN:

152230

Hom.:

583

Cov.:

AF XY:

0.0824

AC XY:

6136

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0830

Gnomad4 AMR

AF:

0.0721

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.0599

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0730

Gnomad4 NFE

AF:

0.0921

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0908

Hom.:

160

Bravo

AF:

0.0850

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Benign:2Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Myeloproliferative neoplasm, unclassifiable

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Dept. of Cytogenetics, ICMR- National Institute of Immunohaematology

Aug 25, 2022

- -

PDGFRA-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary cancer

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

Mar 27, 2024

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.4

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over