1-41482518-A-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The ENST00000372587.5(EDN2):āc.292T>Cā(p.Cys98Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000251 in 1,596,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
EDN2
ENST00000372587.5 missense
ENST00000372587.5 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 6.23
Genes affected
EDN2 (HGNC:3177): (endothelin 2) This gene encodes a member of the endothelin protein family of secretory vasoconstrictive peptides. The preproprotein is processed to a short mature form which functions as a ligand for the endothelin receptors that initiate intracellular signaling events. This gene product is involved in a wide range of biological processes, such as hypertension and ovulation. Altered expression of this gene is implicated in tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.976
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EDN2 | NM_001956.5 | c.292T>C | p.Cys98Arg | missense_variant | 3/5 | ENST00000372587.5 | NP_001947.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EDN2 | ENST00000372587.5 | c.292T>C | p.Cys98Arg | missense_variant | 3/5 | 1 | NM_001956.5 | ENSP00000361668 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000872 AC: 2AN: 229342Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 125534
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GnomAD4 exome AF: 6.93e-7 AC: 1AN: 1443962Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 718386
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2023 | The c.292T>C (p.C98R) alteration is located in exon 3 (coding exon 3) of the EDN2 gene. This alteration results from a T to C substitution at nucleotide position 292, causing the cysteine (C) at amino acid position 98 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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