rs140943817
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_006206.6(PDGFRA):āc.2899C>Gā(p.Leu967Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,611,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L967L) has been classified as Likely benign.
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.2899C>G | p.Leu967Val | missense_variant | 22/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.2899C>G | p.Leu967Val | missense_variant | 22/23 | 1 | NM_006206.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00134 AC: 204AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000318 AC: 80AN: 251258Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135782
GnomAD4 exome AF: 0.000121 AC: 177AN: 1459386Hom.: 0 Cov.: 30 AF XY: 0.000106 AC XY: 77AN XY: 726194
GnomAD4 genome ? AF: 0.00134 AC: 204AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.00128 AC XY: 95AN XY: 74500
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 10, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2018 | The p.L967V variant (also known as c.2899C>G), located in coding exon 21 of the PDGFRA gene, results from a C to G substitution at nucleotide position 2899. The leucine at codon 967 is replaced by valine, an amino acid with highly similar properties. One study detected this alteration in a patient with a congenital diaphragmatic hernia (Bleyl SB et al. Eur. J. Hum. Genet., 2007 Sep;15:950-8). This variant has also been identified in a cohort of 681 ancestrally diverse, healthy subjects. (Bodian DL et al. PLoS ONE, 2014 Apr;9:e94554). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
PDGFRA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 13, 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at