rs878853118

Positions:

• chr2-232485252-GCCCAT-GAGC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_004826.4(ECEL1):​c.797_801delinsGCT​(p.Asp266GlyfsTer15) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ECEL1 NM_004826.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.06

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-232485253-CCCAT-AGC is Pathogenic according to our data. Variant chr2-232485253-CCCAT-AGC is described in ClinVar as [Pathogenic]. Clinvar id is 242402.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECEL1	NM_004826.4	c.797_801delinsGCT	p.Asp266GlyfsTer15	frameshift_variant	3/18	ENST00000304546.6	NP_004817.2
ECEL1	NM_001290787.2	c.797_801delinsGCT	p.Asp266GlyfsTer15	frameshift_variant	3/18		NP_001277716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECEL1	ENST00000304546.6	c.797_801delinsGCT	p.Asp266GlyfsTer15	frameshift_variant	3/18	1	NM_004826.4	ENSP00000302051	P4
ECEL1	ENST00000409941.1	c.797_801delinsGCT	p.Asp266GlyfsTer15	frameshift_variant	2/17	1		ENSP00000386333	A1
ECEL1	ENST00000482346.1	n.1001_1005delinsGCT		non_coding_transcript_exon_variant	3/17	2

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

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

research

University of Washington Center for Mendelian Genomics, University of Washington

Jan 08, 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: rs878853118; hg19: chr2-233349963;