rs4358459

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006206.6(PDGFRA):c.939T>G(p.Gly313Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,613,524 control chromosomes in the GnomAD database, including 20,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2940 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17816 hom. )

Consequence

PDGFRA
NM_006206.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.23

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:

ENSG00000282278 (HGNC:):

ENSG00000282278 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-54267559-T-G is Benign according to our data. Variant chr4-54267559-T-G is described in ClinVar as [Benign]. Clinvar id is 259956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6 link	c.939T>G	p.Gly313Gly	synonymous_variant	Exon 7 of 23	ENST00000257290.10	NP_006197.1	P16234-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDGFRA	ENST00000257290.10 link	c.939T>G	p.Gly313Gly	synonymous_variant	Exon 7 of 23	1	NM_006206.6	ENSP00000257290.5	P16234-1
ENSG00000282278	ENST00000507166.5 link	c.1018-7366T>G		intron_variant	Intron 12 of 23	2		ENSP00000423325.1	A0A0B4J203
PDGFRA	ENST00000509092.5 link	n.757T>G		non_coding_transcript_exon_variant	Exon 6 of 15	1
PDGFRA	ENST00000509490.5 link	n.939T>G		non_coding_transcript_exon_variant	Exon 7 of 18	1		ENSP00000424218.1	P16234-3

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27172

AN:

151930

Hom.:

2937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.185

AC:

46414

AN:

251130

Hom.:

5849

AF XY:

0.175

AC XY:

23786

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.0665

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.143

AC:

209339

AN:

1461476

Hom.:

17816

Cov.:

AF XY:

0.143

AC XY:

103815

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.0722

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.179

AC:

27209

AN:

152048

Hom.:

2940

Cov.:

AF XY:

0.181

AC XY:

13488

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.0651

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.247

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.133

Hom.:

3015

Bravo

AF:

0.193

Asia WGS

AF:

0.247

AC:

859

AN:

3478

EpiCase

AF:

0.113

EpiControl

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Gastrointestinal stromal tumor

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Idiopathic hypereosinophilic syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Hereditary cancer-predisposing syndrome

Benign:1

Nov 08, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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