rs587776918

Variant names:

• chr2-232486298-CTGGCGTCCAGGT-C
• rs587776918
• NM_004826.4:c.344_355delACCTGGACGCCA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM4 PP5

The NM_004826.4(ECEL1):​c.344_355delACCTGGACGCCA​(p.Asn115_Ala118del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ECEL1 NM_004826.4 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.47
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004826.4.
• PP5: Variant 2-232486298-CTGGCGTCCAGGT-C is Pathogenic according to our data. Variant chr2-232486298-CTGGCGTCCAGGT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 39489.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECEL1	NM_004826.4	c.344_355delACCTGGACGCCA	p.Asn115_Ala118del	disruptive_inframe_deletion	Exon 2 of 18	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2	c.344_355delACCTGGACGCCA	p.Asn115_Ala118del	disruptive_inframe_deletion	Exon 2 of 18		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6	c.344_355delACCTGGACGCCA	p.Asn115_Ala118del	disruptive_inframe_deletion	Exon 2 of 18	1	NM_004826.4	ENSP00000302051.1
ECEL1	ENST00000409941.1	c.344_355delACCTGGACGCCA	p.Asn115_Ala118del	disruptive_inframe_deletion	Exon 1 of 17	1		ENSP00000386333.1
ECEL1	ENST00000482346.1	n.548_559delACCTGGACGCCA		non_coding_transcript_exon_variant	Exon 2 of 17	2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Distal arthrogryposis type 5D Pathogenic:1

Jan 10, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5
Mutation Taster		=7/193	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs587776918; hg19: chr2-233351008;