NM_006206.6:c.612T>C

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.612T>C(p.Asn204Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,612,950 control chromosomes in the GnomAD database, including 20,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2986 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17984 hom. )

Consequence

PDGFRA
NM_006206.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.60

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:

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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 4-54263911-T-C is Benign according to our data. Variant chr4-54263911-T-C is described in ClinVar as [Benign]. Clinvar id is 259955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.6 with no splicing effect.

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 rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6 link	c.612T>C	p.Asn204Asn	synonymous_variant	Exon 4 of 23	ENST00000257290.10	NP_006197.1	P16234-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10 link	c.612T>C	p.Asn204Asn	synonymous_variant	Exon 4 of 23	1	NM_006206.6	ENSP00000257290.5		P16234-1
ENSG00000282278	ENST00000507166.5 link	c.1018-11014T>C		intron_variant	Intron 12 of 23	2		ENSP00000423325.1		A0A0B4J203

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27424

AN:

151930

Hom.:

2984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.0702

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.186

AC:

46654

AN:

250530

Hom.:

5884

AF XY:

0.177

AC XY:

23913

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.0712

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.144

AC:

210489

AN:

1460904

Hom.:

17984

Cov.:

AF XY:

0.144

AC XY:

104392

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.0764

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.181

AC:

27462

AN:

152046

Hom.:

2986

Cov.:

AF XY:

0.183

AC XY:

13635

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.0702

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.247

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.147

Hom.:

1214

Bravo

AF:

0.195

Asia WGS

AF:

0.247

AC:

857

AN:

3478

EpiCase

AF:

0.116

EpiControl

AF:

0.114

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

0.092

DANN

Benign

0.70

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

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