chr17-12992841-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018127.7(ELAC2):c.2458G>A(p.Ala820Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. A820G) has been classified as Uncertain significance.
Frequency
Consequence
NM_018127.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELAC2 | NM_018127.7 | c.2458G>A | p.Ala820Thr | missense_variant | 24/24 | ENST00000338034.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELAC2 | ENST00000338034.9 | c.2458G>A | p.Ala820Thr | missense_variant | 24/24 | 1 | NM_018127.7 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151620Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459598Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726148
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151620Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74026
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 28, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with ELAC2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 820 of the ELAC2 protein (p.Ala820Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at