rs587776918

Positions:

• chr2-232486298-CTGGCGTCCAGGT-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 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. 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 id is 39489.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-232486298-CTGGCGTCCAGGT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECEL1	NM_004826.4	c.344_355delACCTGGACGCCA	p.Asn115_Ala118del	disruptive_inframe_deletion	2/18	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2	c.344_355delACCTGGACGCCA	p.Asn115_Ala118del	disruptive_inframe_deletion	2/18		NP_001277716.1

Ensembl

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 10, 2013

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587776918; hg19: chr2-233351008;