chr4-54285388-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001347828.2(PDGFRA):c.2416C>A(p.Leu806Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000949 in 1,474,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. L806H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

PDGFRA
NM_001347828.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.98

Publications

3 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: Genomics England PanelApp, Ambry Genetics, G2P
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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12415862).

BP6

Variant 4-54285388-C-A is Benign according to our data. Variant chr4-54285388-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 575366.

BS2

High AC in GnomAdExome4 at 10 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347828.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRA	NM_006206.6	MANE Select	c.2341C>A	p.Leu781Ile	missense	Exon 17 of 23	NP_006197.1
PDGFRA	NM_001347828.2		c.2416C>A	p.Leu806Ile	missense	Exon 18 of 24	NP_001334757.1
PDGFRA	NM_001347830.2		c.2380C>A	p.Leu794Ile	missense	Exon 17 of 23	NP_001334759.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.2341C>A	p.Leu781Ile	missense	Exon 17 of 23	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	TSL:2	c.1621C>A	p.Leu541Ile	missense	Exon 18 of 24	ENSP00000423325.1
PDGFRA	ENST00000870889.1		c.2341C>A	p.Leu781Ile	missense	Exon 17 of 23	ENSP00000540948.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000119

AC:

AN:

251204

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00000756

AC:

AN:

1322662

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

665700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30786

American (AMR)

AF:

0.0000224

AC:

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25306

East Asian (EAS)

AF:

0.00

AC:

AN:

39078

South Asian (SAS)

AF:

0.0000240

AC:

AN:

83498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5528

European-Non Finnish (NFE)

AF:

0.00000406

AC:

AN:

984750

Other (OTH)

AF:

0.0000358

AC:

AN:

55792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

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:

0.0000263

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.000262

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions as Germline

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)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

-0.18

Eigen_PC

Benign

0.020

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

M_CAP

Benign

0.017

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.82

PhyloP100

4.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.46

REVEL

Benign

0.15

Sift

Benign

0.24

Sift4G

Benign

0.38

Polyphen

0.010

Vest4

0.27

MutPred

0.45

Gain of methylation at K779 (P = 0.0764)

MVP

0.52

MPC

0.39

ClinPred

0.29

GERP RS

5.1

Varity_R

0.29

gMVP

0.33

Mutation Taster

=58/42

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over