4-54280353-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_006206.6(PDGFRA):c.2194A>C(p.Met732Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M732V) has been classified as Uncertain significance.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.2194A>C | p.Met732Leu | missense_variant | 16/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.2194A>C | p.Met732Leu | missense_variant | 16/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000507536.1 | n.620A>C | non_coding_transcript_exon_variant | 4/5 | 1 | ||||
PDGFRA | ENST00000509092.5 | n.2012A>C | non_coding_transcript_exon_variant | 15/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.*115A>C | 3_prime_UTR_variant, NMD_transcript_variant | 17/18 | 1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 732 of the PDGFRA protein (p.Met732Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.