rs9895963

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018127.7(ELAC2):c.155C>T(p.Ser52Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,607,976 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 3 hom. )

Consequence

ELAC2
NM_018127.7 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 0.207

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]

ELAC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005798787).

BP6

Variant 17-13017793-G-A is Benign according to our data. Variant chr17-13017793-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00213 (324/152366) while in subpopulation AFR AF= 0.0068 (283/41588). AF 95% confidence interval is 0.00615. There are 1 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ELAC2	NM_018127.7 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant	1/24	ENST00000338034.9	NP_060597.4
ELAC2	NM_173717.2 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant	1/24		NP_776065.1
ELAC2	NM_001165962.2 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant	1/23		NP_001159434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9 linkuse as main transcript	c.155C>T	p.Ser52Phe	missense_variant	1/24	1	NM_018127.7	ENSP00000337445	P2	Q9BQ52-1

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

323

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00680

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000715

AC:

160

AN:

223824

Hom.:

AF XY:

0.000599

AC XY:

AN XY:

123500

show subpopulations

Gnomad AFR exome

AF:

0.00717

Gnomad AMR exome

AF:

0.000302

Gnomad ASJ exome

AF:

0.00255

Gnomad EAS exome

AF:

0.000469

Gnomad SAS exome

AF:

0.000136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000366

GnomAD4 exome

AF:

0.000376

AC:

548

AN:

1455610

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

237

AN XY:

723740

show subpopulations

Gnomad4 AFR exome

AF:

0.00769

Gnomad4 AMR exome

AF:

0.000386

Gnomad4 ASJ exome

AF:

0.00243

Gnomad4 EAS exome

AF:

0.000355

Gnomad4 SAS exome

AF:

0.000210

Gnomad4 FIN exome

AF:

0.0000583

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.000766

GnomAD4 genome

AF:

0.00213

AC:

324

AN:

152366

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00680

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000471

Hom.:

Bravo

AF:

0.00254

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00370

AC:

ESP6500EA

AF:

0.000352

AC:

ExAC

AF:

0.000691

AC:

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 15, 2020	- -
Uncertain significance, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 29, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Prostate cancer, hereditary, 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Combined oxidative phosphorylation defect type 17

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

ELAC2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.022

T;.;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.27

T;T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.0058

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.2

N;N;N;.

REVEL

Benign

0.057

Sift

Benign

0.047

D;D;T;.

Sift4G

Uncertain

0.054

T;T;T;T

Polyphen

0.29

B;B;.;.

Vest4

0.085

MVP

0.75

MPC

0.20

ClinPred

0.0044

GERP RS

3.1

Varity_R

0.040

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over