rs143344944
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_006206.6(PDGFRA):c.1319C>T(p.Thr440Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,613,932 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T440A) 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 -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.1319C>T | p.Thr440Met | missense_variant | 9/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.1319C>T | p.Thr440Met | missense_variant | 9/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.1137C>T | non_coding_transcript_exon_variant | 8/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.1319C>T | p.Thr440Met | missense_variant, NMD_transcript_variant | 9/18 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152104Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000123 AC: 31AN: 251282Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135808
GnomAD4 exome AF: 0.0000869 AC: 127AN: 1461710Hom.: 0 Cov.: 32 AF XY: 0.0000853 AC XY: 62AN XY: 727172
GnomAD4 genome AF: 0.000105 AC: 16AN: 152222Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5AN XY: 74404
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2019 | 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. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 02, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
PDGFRA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 02, 2024 | 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). - |
Ovarian cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
Gastrointestinal stromal tumor Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at