rs774522904
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_006206.6(PDGFRA):c.3179T>A(p.Ile1060Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1060V) has been classified as Uncertain significance.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.3179T>A | p.Ile1060Asn | missense_variant | 23/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.3179T>A | p.Ile1060Asn | missense_variant | 23/23 | 1 | NM_006206.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152088Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251240Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135778
GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461738Hom.: 0 Cov.: 35 AF XY: 0.0000536 AC XY: 39AN XY: 727186
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152088Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74280
ClinVar
Submissions by phenotype
Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal Uncertain:2Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 31, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Sep 08, 2022 | The PDGFRA c.3179T>A (p.Ile1060Asn) missense change has a maximum subpopulation frequency of 0.0093% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with PDGFRA-associated tumors. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. - |
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 09-29-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 1060 of the PDGFRA protein (p.Ile1060Asn). This variant is present in population databases (rs774522904, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. ClinVar contains an entry for this variant (Variation ID: 240344). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PDGFRA protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 29, 2019 | The p.I1060N variant (also known as c.3179T>A), located in coding exon 22 of the PDGFRA gene, results from a T to A substitution at nucleotide position 3179. The isoleucine at codon 1060 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at