2-232482155-A-G

Variant names:

• chr2-232482155-A-G
• rs909431
• NM_004826.4:c.1796+263T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004826.4(ECEL1):​c.1796+263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,254 control chromosomes in the GnomAD database, including 4,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.23 (4499 hom., cov: 33)
• Consequence: ECEL1 NM_004826.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.55
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• distal arthrogryposis type 5D

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-232482155-A-G is Benign according to our data. Variant chr2-232482155-A-G is described in ClinVar as Benign. ClinVar VariationId is 1238548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECEL1	NM_004826.4	c.1796+263T>C		intron_variant	Intron 12 of 17	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2	c.1790+263T>C		intron_variant	Intron 12 of 17		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6	c.1796+263T>C		intron_variant	Intron 12 of 17	1	NM_004826.4	ENSP00000302051.1
ECEL1	ENST00000409941.1	c.1790+263T>C		intron_variant	Intron 11 of 16	1		ENSP00000386333.1
ECEL1	ENST00000411860.5	c.41+263T>C		intron_variant	Intron 1 of 5	3		ENSP00000412683.1
ECEL1	ENST00000482346.1	n.2107+263T>C		intron_variant	Intron 11 of 16	2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34953 AN: 152136 Hom.: 4481 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 35006 AN: 152254 Hom.: 4499 Cov.: 33 AF XY: 0.234 AC XY: 17406 AN XY: 74440

African (AFR) AF: 0.145 AC: 6021 AN: 41550

American (AMR) AF: 0.287 AC: 4394 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2341 AN: 5176

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4828

European-Finnish (FIN) AF: 0.311 AC: 3298 AN: 10606

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16272 AN: 68008

Other (OTH) AF: 0.202 AC: 427 AN: 2114

Alfa AF: 0.234 Hom.: 13180

Bravo AF: 0.229

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.024
DANN	Benign	0.33
PhyloP100		-4.5
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs909431; hg19: chr2-233346865;