NM_018127.7:c.1985T>C
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_018127.7(ELAC2):c.1985T>C(p.Val662Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V662V) has been classified as Likely benign.
Frequency
Consequence
NM_018127.7 missense
Scores
Clinical Significance
Conservation
Publications
- combined oxidative phosphorylation defect type 17Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- mitochondrial diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELAC2 | NM_018127.7 | c.1985T>C | p.Val662Ala | missense_variant | Exon 21 of 24 | ENST00000338034.9 | NP_060597.4 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461718Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727162 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 17 Uncertain:1
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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 474563). This variant has not been reported in the literature in individuals affected with ELAC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 662 of the ELAC2 protein (p.Val662Ala). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at