rs2127996298
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003376.6(VEGFA):c.274C>A(p.Pro92Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P92S) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
VEGFA
NM_003376.6 missense
NM_003376.6 missense
Scores
5
12
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.56
Publications
0 publications found
Genes affected
VEGFA (HGNC:12680): (vascular endothelial growth factor A) This gene is a member of the PDGF/VEGF growth factor family. It encodes a heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells, and is essential for both physiological and pathological angiogenesis. Disruption of this gene in mice resulted in abnormal embryonic blood vessel formation. This gene is upregulated in many known tumors and its expression is correlated with tumor stage and progression. Elevated levels of this protein are found in patients with POEMS syndrome, also known as Crow-Fukase syndrome. Allelic variants of this gene have been associated with microvascular complications of diabetes 1 (MVCD1) and atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been described. There is also evidence for alternative translation initiation from upstream non-AUG (CUG) codons resulting in additional isoforms. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is antiangiogenic. Expression of some isoforms derived from the AUG start codon is regulated by a small upstream open reading frame, which is located within an internal ribosome entry site. The levels of VEGF are increased during infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus promoting inflammation by facilitating recruitment of inflammatory cells, and by increasing the level of angiopoietin II (Ang II), one of two products of the SARS-CoV-2 binding target, angiotensin-converting enzyme 2 (ACE2). In turn, Ang II facilitates the elevation of VEGF, thus forming a vicious cycle in the release of inflammatory cytokines. [provided by RefSeq, Jun 2020]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08692017).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| VEGFA | ENST00000672860.3 | c.274C>A | p.Pro92Thr | missense_variant | Exon 1 of 8 | NM_003376.6 | ENSP00000500082.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1390522Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 685730
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1390522
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
685730
African (AFR)
AF:
AC:
0
AN:
30582
American (AMR)
AF:
AC:
0
AN:
35208
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24962
East Asian (EAS)
AF:
AC:
0
AN:
35056
South Asian (SAS)
AF:
AC:
0
AN:
78220
European-Finnish (FIN)
AF:
AC:
0
AN:
48066
Middle Eastern (MID)
AF:
AC:
0
AN:
4170
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1076622
Other (OTH)
AF:
AC:
0
AN:
57636
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;.;.;.;.;.;T;.;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;.;.;.;.;.;N;N;.;N;N;N
REVEL
Benign
Sift
Uncertain
D;.;D;D;.;.;.;.;.;D;D;.;D;D;D
Sift4G
Uncertain
D;.;D;D;D;D;.;D;.;D;D;D;D;D;D
Polyphen
0.26, 0.64, 0.016
.;.;.;.;B;P;.;P;B;.;.;.;.;.;.
MutPred
Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);Gain of phosphorylation at P92 (P = 4e-04);
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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