rs1553566820
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_004826.4(ECEL1):c.1797-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Consequence
ECEL1
NM_004826.4 splice_region, splice_polypyrimidine_tract, intron
NM_004826.4 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9990
2
Clinical Significance
Conservation
PhyloP100: -0.278
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 2-232481857-C-T is Pathogenic according to our data. Variant chr2-232481857-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 435021.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ECEL1 | NM_004826.4 | c.1797-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000304546.6 | |||
ECEL1 | NM_001290787.2 | c.1791-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ECEL1 | ENST00000304546.6 | c.1797-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004826.4 | P4 | |||
ECEL1 | ENST00000409941.1 | c.1791-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | A1 | ||||
ECEL1 | ENST00000411860.5 | c.42-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 3 | |||||
ECEL1 | ENST00000482346.1 | n.2108-8G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Cov.: 38
GnomAD4 exome
Cov.:
38
GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Distal arthrogryposis type 5D Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 05, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
DS_AL_spliceai
Position offset: -8
Find out detailed SpliceAI scores and Pangolin per-transcript scores at