4-54289105-A-G
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_006206.6(PDGFRA):āc.2871A>Gā(p.Gln957=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000926 in 1,576,334 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00034 ( 1 hom., cov: 32)
Exomes š: 0.000066 ( 0 hom. )
Consequence
PDGFRA
NM_006206.6 synonymous
NM_006206.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.310
Genes affected
PDGFRA (HGNC:8803): (platelet derived growth factor receptor alpha) This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 4-54289105-A-G is Benign according to our data. Variant chr4-54289105-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 407414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.31 with no splicing effect.
BS2
High AC in GnomAd4 at 52 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.2871A>G | p.Gln957= | synonymous_variant | 21/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.2871A>G | p.Gln957= | synonymous_variant | 21/23 | 1 | NM_006206.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152114Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000139 AC: 35AN: 251126Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135682
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GnomAD4 exome AF: 0.0000660 AC: 94AN: 1424220Hom.: 0 Cov.: 25 AF XY: 0.0000577 AC XY: 41AN XY: 711082
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GnomAD4 genome AF: 0.000342 AC: 52AN: 152114Hom.: 1 Cov.: 32 AF XY: 0.000498 AC XY: 37AN XY: 74290
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 23, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | PDGFRA: BP4, BP7 - |
Gastrointestinal stromal tumor Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at