rs761446758
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_006206.6(PDGFRA):c.629C>A(p.Ala210Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000206 in 1,459,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. A210V) has been classified as Uncertain significance.
Frequency
Consequence
NM_006206.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.629C>A | p.Ala210Glu | missense_variant, splice_region_variant | 5/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.629C>A | p.Ala210Glu | missense_variant, splice_region_variant | 5/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000508170.5 | c.*963C>A | 3_prime_UTR_variant | 4/4 | 1 | ||||
PDGFRA | ENST00000509092.5 | n.447C>A | splice_region_variant, non_coding_transcript_exon_variant | 4/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.629C>A | p.Ala210Glu | missense_variant, splice_region_variant, NMD_transcript_variant | 5/18 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459438Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726092
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
PDGFRA-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 06, 2023 | The PDGFRA c.629C>A variant is predicted to result in the amino acid substitution p.Ala210Glu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. 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 | Jan 19, 2017 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PDGFRA-related disease. This sequence change replaces alanine with glutamic acid at codon 210 of the PDGFRA protein (p.Ala210Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at