4-54263931-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000508170.5(PDGFRA):c.632C>T(p.Thr211Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,612,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T211A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PDGFRA
ENST00000508170.5 missense

Scores

Splicing: ADA: 0.00008568

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.610

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

gastrointestinal stromal tumor
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
polyps, multiple and recurrent inflammatory fibroid, gastrointestinal
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
isolated cleft palate
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PDGFRA links:

ENSG00000282278 (HGNC:):

ENSG00000282278 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06386313).

BP6

Variant 4-54263931-C-T is Benign according to our data. Variant chr4-54263931-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 240355.

BS2

High AC in GnomAd4 at 21 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000508170.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDGFRA	NM_006206.6	MANE Select	c.628+4C>T	splice_region intron	N/A	NP_006197.1	P16234-1
PDGFRA	NM_001347828.2		c.703+4C>T	splice_region intron	N/A	NP_001334757.1
PDGFRA	NM_001347830.2		c.667+4C>T	splice_region intron	N/A	NP_001334759.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDGFRA	ENST00000508170.5	TSL:1	c.632C>T	p.Thr211Ile	missense	Exon 4 of 4	ENSP00000425648.1	P16234-2
PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.628+4C>T		splice_region intron	N/A	ENSP00000257290.5	P16234-1
ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-10994C>T		intron	N/A	ENSP00000423325.1	A0A0B4J203

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000401

AC:

AN:

249068

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460546

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726634

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

33452

American (AMR)

AF:

0.0000448

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111260

Other (OTH)

AF:

0.0000497

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.000458

AC:

AN:

41482

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gastrointestinal stromal tumor (1)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.7

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.20

M_CAP

Benign

0.0088

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

PhyloP100

-0.61

PROVEAN

Benign

-1.6

REVEL

Benign

0.069

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.068

MVP

0.37

ClinPred

0.038

GERP RS

-1.0

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000086

dbscSNV1_RF

Benign

0.13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over