rs1377575423
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_018127.7(ELAC2):c.2445_2447delAGA(p.Glu816del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
ELAC2
NM_018127.7 disruptive_inframe_deletion
NM_018127.7 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.35
Publications
0 publications found
Genes affected
ELAC2 (HGNC:14198): (elaC ribonuclease Z 2) The protein encoded by this gene has a C-terminal domain with tRNA 3′ processing endoribonuclease activity, which catalyzes the removal of the 3' trailer from precursor tRNAs. The protein also interacts with activated Smad family member 2 (Smad2) and its nuclear partner forkhead box H1 (also known as FAST-1), and reduced expression can suppress transforming growth factor-beta induced growth arrest. Mutations in this gene result in an increased risk of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
ELAC2 Gene-Disease associations (from GenCC):
- combined oxidative phosphorylation defect type 17Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
- mitochondrial diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_018127.7. Strenght limited to Supporting due to length of the change: 1aa.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018127.7. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ELAC2 | NM_018127.7 | MANE Select | c.2445_2447delAGA | p.Glu816del | disruptive_inframe_deletion | Exon 24 of 24 | NP_060597.4 | ||
| ELAC2 | NM_173717.2 | c.2442_2444delAGA | p.Glu815del | disruptive_inframe_deletion | Exon 24 of 24 | NP_776065.1 | |||
| ELAC2 | NM_001165962.2 | c.2325_2327delAGA | p.Glu776del | disruptive_inframe_deletion | Exon 23 of 23 | NP_001159434.1 | Q9BQ52-4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ELAC2 | ENST00000338034.9 | TSL:1 MANE Select | c.2445_2447delAGA | p.Glu816del | disruptive_inframe_deletion | Exon 24 of 24 | ENSP00000337445.4 | Q9BQ52-1 | |
| ELAC2 | ENST00000923774.1 | c.2547_2549delAGA | p.Glu850del | disruptive_inframe_deletion | Exon 25 of 25 | ENSP00000593833.1 | |||
| ELAC2 | ENST00000860253.1 | c.2469_2471delAGA | p.Glu824del | disruptive_inframe_deletion | Exon 25 of 25 | ENSP00000530312.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152154
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461578Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 727126 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1461578
Hom.:
AF XY:
AC XY:
4
AN XY:
727126
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53116
Middle Eastern (MID)
AF:
AC:
1
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1112004
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.539
Heterozygous variant carriers
0
1
2
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0.20
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74326 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152154
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74326
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41450
American (AMR)
AF:
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5150
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68034
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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4
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10
<30
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Combined oxidative phosphorylation defect type 17 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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