2-232482880-C-T

Position:

chr2-232482880-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004826.4(ECEL1):c.1656G>A(p.Lys552=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,614,200 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 32 hom. )

Consequence

ECEL1
NM_004826.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.29

Variant links:

Genes affected

ECEL1 (HGNC:3147): (endothelin converting enzyme like 1) This gene encodes a member of the M13 family of endopeptidases. Members of this family are zinc-containing type II integral-membrane proteins that are important regulators of neuropeptide and peptide hormone activity. Mutations in this gene are associated with autosomal recessive distal arthrogryposis, type 5D. This gene has multiple pseudogenes on chromosome 2. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ECEL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 2-232482880-C-T is Benign according to our data. Variant chr2-232482880-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 210908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232482880-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0044 (671/152404) while in subpopulation NFE AF= 0.00707 (481/68048). AF 95% confidence interval is 0.00655. There are 1 homozygotes in gnomad4. There are 301 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECEL1	NM_004826.4 linkuse as main transcript	c.1656G>A	p.Lys552=	synonymous_variant	10/18	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2 linkuse as main transcript	c.1656G>A	p.Lys552=	synonymous_variant	10/18		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6 linkuse as main transcript	c.1656G>A	p.Lys552=	synonymous_variant	10/18	1	NM_004826.4	ENSP00000302051	P4	O95672-1
ECEL1	ENST00000409941.1 linkuse as main transcript	c.1656G>A	p.Lys552=	synonymous_variant	9/17	1		ENSP00000386333	A1	O95672-2
ECEL1	ENST00000482346.1 linkuse as main transcript	n.1967G>A		non_coding_transcript_exon_variant	9/17	2

Frequencies

GnomAD3 genomes

AF:

0.00441

AC:

671

AN:

152286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00707

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00357

AC:

898

AN:

251410

Hom.:

AF XY:

0.00372

AC XY:

505

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.00615

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00606

AC:

8852

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

4233

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00169

Gnomad4 NFE exome

AF:

0.00737

Gnomad4 OTH exome

AF:

0.00555

GnomAD4 genome

AF:

0.00440

AC:

671

AN:

152404

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74530

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00707

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00522

Hom.:

Bravo

AF:

0.00490

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	ECEL1: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 08, 2020	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 20, 2015	- -

ECEL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 14, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.67

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