2-232481836-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004826.4(ECEL1):c.1810G>A(p.Gly604Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/23 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G604W) has been classified as Uncertain significance.
Frequency
Consequence
NM_004826.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ECEL1 | NM_004826.4 | c.1810G>A | p.Gly604Arg | missense_variant | 13/18 | ENST00000304546.6 | |
ECEL1 | NM_001290787.2 | c.1804G>A | p.Gly602Arg | missense_variant | 13/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ECEL1 | ENST00000304546.6 | c.1810G>A | p.Gly604Arg | missense_variant | 13/18 | 1 | NM_004826.4 | P4 | |
ECEL1 | ENST00000409941.1 | c.1804G>A | p.Gly602Arg | missense_variant | 12/17 | 1 | A1 | ||
ECEL1 | ENST00000411860.5 | c.55G>A | p.Gly19Arg | missense_variant | 2/6 | 3 | |||
ECEL1 | ENST00000482346.1 | n.2121G>A | non_coding_transcript_exon_variant | 12/17 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251132Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135836
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461626Hom.: 0 Cov.: 38 AF XY: 0.00000550 AC XY: 4AN XY: 727134
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Distal arthrogryposis type 5D Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | 3billion | Sep 01, 2022 | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.95; 3Cnet: 0.78). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with ECEL1 -related disorder (PMID: 32566668). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at