Variant 3-184278198-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001100121.2(ECE2):c.635A>G(p.Asp212Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ECE2
NM_001100121.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECE2	NM_001100121.2 linkuse as main transcript	c.635A>G	p.Asp212Gly	missense_variant	6/19	ENST00000404464.8	NP_001093591.1	P0DPD6-2P0DPD8
EEF1AKMT4-ECE2	NM_014693.4 linkuse as main transcript	c.989A>G	p.Asp330Gly	missense_variant	6/19		NP_055508.3	P0DPD6P0DPD8-1
ECE2	NM_001100120.2 linkuse as main transcript	c.773A>G	p.Asp258Gly	missense_variant	6/19		NP_001093590.1	P0DPD6-4P0DPD8
ECE2	NM_001037324.3 linkuse as main transcript	c.548A>G	p.Asp183Gly	missense_variant	5/18		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.635A>G	p.Asp212Gly	missense_variant	6/19	1	NM_001100121.2	ENSP00000385846.3		P0DPD6-2
EEF1AKMT4-ECE2	ENST00000402825.7 linkuse as main transcript	c.989A>G	p.Asp330Gly	missense_variant	6/19	1		ENSP00000384223.3		P0DPD8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251422

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

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 12, 2022

The c.989A>G (p.D330G) alteration is located in exon 6 (coding exon 6) of the ECE2 gene. This alteration results from a A to G substitution at nucleotide position 989, causing the aspartic acid (D) at amino acid position 330 to be replaced by a glycine (G). 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

0.10

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;.;.;.;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

T;T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.57

D;D;D;D;D

MetaSVM

Uncertain

0.032

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.3

N;N;N;N;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.016

D;T;D;D;D

Sift4G

Benign

0.073

T;T;T;T;T

Vest4

0.36

MutPred

0.69

Gain of helix (P = 0.2294);.;.;.;.;

MVP

0.83

MPC

0.35

ClinPred

0.60

GERP RS

4.0

Varity_R

0.19

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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