rs387906327
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000338034.9(ELAC2):c.1641_1642insG(p.His548AlafsTer68) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,890 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. L547L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000338034.9 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ELAC2 | NM_018127.7 | c.1641_1642insG | p.His548AlafsTer68 | frameshift_variant | 17/24 | ENST00000338034.9 | NP_060597.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ELAC2 | ENST00000338034.9 | c.1641_1642insG | p.His548AlafsTer68 | frameshift_variant | 17/24 | 1 | NM_018127.7 | ENSP00000337445 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461682Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727152
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Prostate cancer, hereditary, 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2001 | - - |
Combined oxidative phosphorylation defect type 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 23, 2018 | This sequence change creates a premature translational stop signal (p.His548Alafs*68) in the ELAC2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ELAC2-related disease. ClinVar contains an entry for this variant (Variation ID: 5057). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ELAC2 cause disease. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at