rs41279521
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_006206.6(PDGFRA):c.1127G>A(p.Arg376Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,594,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R376G) has been classified as Uncertain significance.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.1127G>A | p.Arg376Gln | missense_variant | 8/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.1127G>A | p.Arg376Gln | missense_variant | 8/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.945G>A | non_coding_transcript_exon_variant | 7/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.1127G>A | p.Arg376Gln | missense_variant, NMD_transcript_variant | 8/18 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000427 AC: 65AN: 152116Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000155 AC: 39AN: 250908Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135620
GnomAD4 exome AF: 0.000101 AC: 146AN: 1441778Hom.: 0 Cov.: 27 AF XY: 0.000100 AC XY: 72AN XY: 718678
GnomAD4 genome ? AF: 0.000427 AC: 65AN: 152234Hom.: 0 Cov.: 31 AF XY: 0.000417 AC XY: 31AN XY: 74412
ClinVar
Submissions by phenotype
PDGFRA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 10, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Gastrointestinal stromal tumor Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at