chr4-54290368-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_006206.6(PDGFRA):c.2936G>A(p.Arg979His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,611,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R979C) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.2936G>A | p.Arg979His | missense_variant | 22/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.2936G>A | p.Arg979His | missense_variant | 22/23 | 1 | NM_006206.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251302Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135804
GnomAD4 exome AF: 0.0000432 AC: 63AN: 1459686Hom.: 0 Cov.: 31 AF XY: 0.0000386 AC XY: 28AN XY: 726296
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74376
ClinVar
Submissions by phenotype
Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 09, 2023 | - - |
PDGFRA-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 07, 2023 | The PDGFRA c.2936G>A variant is predicted to result in the amino acid substitution p.Arg979His. This variant has been reported in an individual from a healthy, ancestrally diverse genome sequencing cohort (Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.0053% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-55156535-G-A). It has conflicting interpretations of likely benign and uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/135020/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 979 of the PDGFRA protein (p.Arg979His). This variant is present in population databases (rs587778598, gnomAD 0.006%). 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: 135020). 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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2019 | 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. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at