Variant 3-184277016-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001100121.2(ECE2):c.251A>G(p.Gln84Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Consequence

ECE2
NM_001100121.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

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]

ECE2 links:

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]

EEF1AKMT4-ECE2 links:

ECE2 (HGNC:):

ECE2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3542667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE2	NM_001100121.2 linkuse as main transcript	c.251A>G	p.Gln84Arg	missense_variant	3/19	ENST00000404464.8	NP_001093591.1	P0DPD6-2P0DPD8
EEF1AKMT4-ECE2	NM_014693.4 linkuse as main transcript	c.605A>G	p.Gln202Arg	missense_variant	3/19		NP_055508.3	P0DPD6P0DPD8-1
ECE2	NM_001100120.2 linkuse as main transcript	c.389A>G	p.Gln130Arg	missense_variant	3/19		NP_001093590.1	P0DPD6-4P0DPD8
ECE2	NM_001037324.3 linkuse as main transcript	c.164A>G	p.Gln55Arg	missense_variant	2/18		NP_001032401.1	P0DPD6-3P0DPD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECE2	ENST00000404464.8 linkuse as main transcript	c.251A>G	p.Gln84Arg	missense_variant	3/19	1	NM_001100121.2	ENSP00000385846.3		P0DPD6-2
EEF1AKMT4-ECE2	ENST00000402825.7 linkuse as main transcript	c.605A>G	p.Gln202Arg	missense_variant	3/19	1		ENSP00000384223.3		P0DPD8-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

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

Aug 02, 2023

The c.605A>G (p.Q202R) alteration is located in exon 3 (coding exon 3) of the ECE2 gene. This alteration results from a A to G substitution at nucleotide position 605, causing the glutamine (Q) at amino acid position 202 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

.;.;.;.;T

Eigen

Benign

-0.091

Eigen_PC

Benign

0.096

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.85

T;T;D;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.35

T;T;T;T;T

MetaSVM

Benign

-0.51

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.095

T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T

Vest4

0.33

MutPred

0.56

Gain of sheet (P = 0.0036);.;.;.;.;

MVP

0.74

MPC

0.21

ClinPred

0.24

GERP RS

5.0

Varity_R

0.23

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over