4-54287544-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_006206.6(PDGFRA):c.2674+3A>G variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,001,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006206.6 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.2674+3A>G | splice_region_variant, intron_variant | 1 | NM_006206.6 | ENSP00000257290.5 | ||||
ENSG00000282278 | ENST00000507166.5 | c.1954+3A>G | splice_region_variant, intron_variant | 2 | ENSP00000423325.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250884Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135652
GnomAD4 exome AF: 0.0000180 AC: 18AN: 1001100Hom.: 0 Cov.: 15 AF XY: 0.0000251 AC XY: 13AN XY: 518616
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 16, 2023 | This sequence change falls in intron 19 of the PDGFRA gene. It does not directly change the encoded amino acid sequence of the PDGFRA protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs765356009, gnomAD 0.02%). 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: 459063). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2024 | This alteration is classified as 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at