rs771421611

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_006206.6(PDGFRA):​c.2574C>A​(p.Pro858Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000465 in 1,291,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P858P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000046 ( 0 hom. )

Consequence

PDGFRA
NM_006206.6 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -3.40

Publications

2 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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 4-54287441-C-A is Benign according to our data. Variant chr4-54287441-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 348906.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].
BP7
Synonymous conserved (PhyloP=-3.4 with no splicing effect.
BS2
High AC in GnomAdExome4 at 6 Unknown,AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDGFRANM_006206.6 linkc.2574C>A p.Pro858Pro synonymous_variant Exon 19 of 23 ENST00000257290.10 NP_006197.1 P16234-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDGFRAENST00000257290.10 linkc.2574C>A p.Pro858Pro synonymous_variant Exon 19 of 23 1 NM_006206.6 ENSP00000257290.5 P16234-1
ENSG00000282278ENST00000507166.5 linkc.1854C>A p.Pro618Pro synonymous_variant Exon 20 of 24 2 ENSP00000423325.1 A0A0B4J203

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000399
AC:
1
AN:
250396
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000465
AC:
6
AN:
1291210
Hom.:
0
Cov.:
20
AF XY:
0.00000153
AC XY:
1
AN XY:
651864
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
30090
American (AMR)
AF:
0.00
AC:
0
AN:
44532
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25060
East Asian (EAS)
AF:
0.000154
AC:
6
AN:
38912
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82862
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53328
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5462
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
956292
Other (OTH)
AF:
0.00
AC:
0
AN:
54672
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.517
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
33

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Gastrointestinal stromal tumor Uncertain:1Benign:1
Dec 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Idiopathic hypereosinophilic syndrome Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1
Dec 18, 2022
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
0.0060
DANN
Benign
0.43
PhyloP100
-3.4
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs771421611; hg19: chr4-55153608; API