17-13000190-G-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_018127.7(ELAC2):​c.1389C>G​(p.Tyr463*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ELAC2
NM_018127.7 stop_gained

Scores

1
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ELAC2NM_018127.7 linkc.1389C>G p.Tyr463* stop_gained Exon 15 of 24 ENST00000338034.9 NP_060597.4 Q9BQ52-1A0A0S2Z5M8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ELAC2ENST00000338034.9 linkc.1389C>G p.Tyr463* stop_gained Exon 15 of 24 1 NM_018127.7 ENSP00000337445.4 Q9BQ52-1
ELAC2ENST00000446899.5 linkc.726C>G p.Tyr242* stop_gained Exon 9 of 10 5 ENSP00000406192.1 H7C2I4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251366
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461686
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727140
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.024
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
27
DANN
Benign
0.94
Eigen
Benign
-0.56
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.25
N
Vest4
0.73
ClinPred
0.93
D
GERP RS
-8.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77972324; hg19: chr17-12903507; API