rs377699966
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_006206.6(PDGFRA):āc.738A>Gā(p.Gln246=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000092 ( 0 hom., cov: 32)
Exomes š: 0.000017 ( 0 hom. )
Consequence
PDGFRA
NM_006206.6 synonymous
NM_006206.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.958
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 4-54265028-A-G is Benign according to our data. Variant chr4-54265028-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 240360.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.958 with no splicing effect.
BS2
?
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.738A>G | p.Gln246= | synonymous_variant | 5/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.738A>G | p.Gln246= | synonymous_variant | 5/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000508170.5 | c.*1072A>G | 3_prime_UTR_variant | 4/4 | 1 | ||||
PDGFRA | ENST00000509092.5 | n.556A>G | non_coding_transcript_exon_variant | 4/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.738A>G | p.Gln246= | synonymous_variant, NMD_transcript_variant | 5/18 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251402Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135864
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461544Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727082
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74438
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 15, 2021 | - - |
PDGFRA-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 28, 2023 | The PDGFRA c.738A>G variant is not predicted to result in an amino acid change (p.=). This variant is predicted to create a cryptic splice site (Alamut Visual Plus v1.6.1). However, in silico splicing predictions programs are not equivalent to functional evidence. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. This variant has been interpreted as likely benign by multiple submitters in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/240360/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 25, 2023 | - - |
Gastrointestinal stromal tumor Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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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