rs149561185
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_018127.7(ELAC2):c.1924G>A(p.Val642Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000694 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V642V) has been classified as Likely benign.
Frequency
Consequence
NM_018127.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ELAC2 | NM_018127.7 | c.1924G>A | p.Val642Met | missense_variant | 21/24 | ENST00000338034.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ELAC2 | ENST00000338034.9 | c.1924G>A | p.Val642Met | missense_variant | 21/24 | 1 | NM_018127.7 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251348Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135860
GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461762Hom.: 0 Cov.: 32 AF XY: 0.0000509 AC XY: 37AN XY: 727180
GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74352
ClinVar
Submissions by phenotype
Prostate cancer, hereditary, 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Combined oxidative phosphorylation defect type 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 642 of the ELAC2 protein (p.Val642Met). This variant is present in population databases (rs149561185, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ELAC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 576991). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 25, 2023 | PP3 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at