4-54261246-C-T

Position:

chr4-54261246-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006206.6(PDGFRA):c.201C>T(p.Ser67=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,614,014 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0033 ( 4 hom. )

Consequence

PDGFRA
NM_006206.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0990

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 4-54261246-C-T is Benign according to our data. Variant chr4-54261246-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 240322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-54261246-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.099 with no splicing effect.

BS2

High AC in GnomAd4 at 617 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRA	NM_006206.6 linkuse as main transcript	c.201C>T	p.Ser67=	synonymous_variant	3/23	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10 linkuse as main transcript	c.201C>T	p.Ser67=	synonymous_variant	3/23	1	NM_006206.6	ENSP00000257290	P1	P16234-1

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

618

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00720

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00840

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00298

AC:

750

AN:

251376

Hom.:

AF XY:

0.00280

AC XY:

380

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00824

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00882

Gnomad NFE exome

AF:

0.00321

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00328

AC:

4789

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

2310

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00854

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00878

Gnomad4 NFE exome

AF:

0.00339

Gnomad4 OTH exome

AF:

0.00311

GnomAD4 genome

AF:

0.00406

AC:

617

AN:

152146

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00716

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00840

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00362

Hom.:

Bravo

AF:

0.00399

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00245

EpiControl

AF:

0.00196

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	PDGFRA: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2021	- -

Gastrointestinal stromal tumor

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	curation	Sema4, Sema4	Oct 22, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 27, 2018	This alteration is classified as likely 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. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 13, 2021

- -

Idiopathic hypereosinophilic syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.1

DANN

Benign

0.62

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