Variant chr3-184278219-T-C 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.656T>C(p.Val219Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ECE2
NM_001100121.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

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.656T>C	p.Val219Ala	missense_variant	6/19	ENST00000404464.8	NP_001093591.1	P0DPD6-2P0DPD8
EEF1AKMT4-ECE2	NM_014693.4 linkuse as main transcript	c.1010T>C	p.Val337Ala	missense_variant	6/19		NP_055508.3	P0DPD6P0DPD8-1
ECE2	NM_001100120.2 linkuse as main transcript	c.794T>C	p.Val265Ala	missense_variant	6/19		NP_001093590.1	P0DPD6-4P0DPD8
ECE2	NM_001037324.3 linkuse as main transcript	c.569T>C	p.Val190Ala	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.656T>C	p.Val219Ala	missense_variant	6/19	1	NM_001100121.2	ENSP00000385846.3		P0DPD6-2
EEF1AKMT4-ECE2	ENST00000402825.7 linkuse as main transcript	c.1010T>C	p.Val337Ala	missense_variant	6/19	1		ENSP00000384223.3		P0DPD8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251430

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 08, 2022

The c.1010T>C (p.V337A) alteration is located in exon 6 (coding exon 6) of the ECE2 gene. This alteration results from a T to C substitution at nucleotide position 1010, causing the valine (V) at amino acid position 337 to be replaced by an alanine (A). 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

0.31

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;.;.;.;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.66

D;D;D;D;D

MetaSVM

Benign

-0.70

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.3

N;N;N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.18

T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T

Vest4

0.57

MutPred

0.68

Loss of stability (P = 0.1728);.;.;.;.;

MVP

0.74

MPC

0.78

ClinPred

0.70

GERP RS

5.2

Varity_R

0.16

gMVP

0.64

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