GeneBe

rs768882428

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001100121.2(ECE2):​c.628C>A​(p.Pro210Thr) 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. 16/21 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. P210S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ECE2
NM_001100121.2 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.771

Publications

1 publications found
Variant links:
Genes affected
ECE2 (HGNC:13275): (endothelin converting enzyme 2) Enables metalloendopeptidase activity. Involved in peptide hormone processing. Located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]
EEF1AKMT4-ECE2 (HGNC:53615): (EEF1AKMT4-ECE2 readthrough) This gene represents naturally occurring readthrough transcription between adjacent genes eukaryotic translation elongation factor 1 alpha lysine methyltransferase 4 (GeneID: 110599564) and endothelin converting enzyme 2 (GeneID:9718). The readthrough transcript representing this gene encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

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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=0.17297223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100121.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ECE2
NM_001100121.2
MANE Select
c.628C>Ap.Pro210Thr
missense
Exon 6 of 19NP_001093591.1P0DPD6-2
EEF1AKMT4-ECE2
NM_014693.4
c.982C>Ap.Pro328Thr
missense
Exon 6 of 19NP_055508.3
ECE2
NM_001100120.2
c.766C>Ap.Pro256Thr
missense
Exon 6 of 19NP_001093590.1P0DPD6-4

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ECE2
ENST00000404464.8
TSL:1 MANE Select
c.628C>Ap.Pro210Thr
missense
Exon 6 of 19ENSP00000385846.3P0DPD6-2
EEF1AKMT4-ECE2
ENST00000402825.7
TSL:1
c.982C>Ap.Pro328Thr
missense
Exon 6 of 19ENSP00000384223.3P0DPD8-1
ECE2
ENST00000357474.9
TSL:1
c.766C>Ap.Pro256Thr
missense
Exon 6 of 19ENSP00000350066.5P0DPD6-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
63
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.21
T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.57
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.94
T
PhyloP100
0.77
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.034
Sift
Benign
0.14
T
Sift4G
Benign
0.30
T
Vest4
0.18
MutPred
0.42
Loss of catalytic residue at W329 (P = 0.0448)
MVP
0.68
MPC
0.30
ClinPred
0.16
T
GERP RS
1.3
Varity_R
0.085
gMVP
0.44
Mutation Taster
=90/10
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs768882428; hg19: chr3-183995979; API