rs5030739

Positions:

chr17-12996585-C-T

Variant summary

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

The NM_018127.7(ELAC2):c.1621G>A(p.Ala541Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0371 in 1,614,038 control chromosomes in the GnomAD database, including 1,293 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 97 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1196 hom. )

Consequence

ELAC2
NM_018127.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:10

Conservation

PhyloP100: 3.67

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=0.009242713).

BP6

Variant 17-12996585-C-T is Benign according to our data. Variant chr17-12996585-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 5056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-12996585-C-T is described in Lovd as [Benign]. Variant chr17-12996585-C-T is described in Lovd as [Pathogenic].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0293 (4465/152274) while in subpopulation SAS AF= 0.0429 (207/4828). AF 95% confidence interval is 0.0385. There are 97 homozygotes in gnomad4. There are 2183 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 97 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAC2	NM_018127.7 linkuse as main transcript	c.1621G>A	p.Ala541Thr	missense_variant	17/24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9 linkuse as main transcript	c.1621G>A	p.Ala541Thr	missense_variant	17/24	1	NM_018127.7	ENSP00000337445	P2	Q9BQ52-1

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

4467

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00603

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.0588

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0422

Gnomad FIN

AF:

0.0437

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0347

AC:

8725

AN:

251120

Hom.:

190

AF XY:

0.0358

AC XY:

4859

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00511

Gnomad AMR exome

AF:

0.0301

Gnomad ASJ exome

AF:

0.0506

Gnomad EAS exome

AF:

0.00669

Gnomad SAS exome

AF:

0.0439

Gnomad FIN exome

AF:

0.0439

Gnomad NFE exome

AF:

0.0390

Gnomad OTH exome

AF:

0.0408

GnomAD4 exome

AF:

0.0379

AC:

55441

AN:

1461764

Hom.:

1196

Cov.:

AF XY:

0.0383

AC XY:

27818

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00588

Gnomad4 AMR exome

AF:

0.0293

Gnomad4 ASJ exome

AF:

0.0560

Gnomad4 EAS exome

AF:

0.00398

Gnomad4 SAS exome

AF:

0.0451

Gnomad4 FIN exome

AF:

0.0462

Gnomad4 NFE exome

AF:

0.0391

Gnomad4 OTH exome

AF:

0.0367

GnomAD4 genome

AF:

0.0293

AC:

4465

AN:

152274

Hom.:

Cov.:

AF XY:

0.0293

AC XY:

2183

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00601

Gnomad4 AMR

AF:

0.0308

Gnomad4 ASJ

AF:

0.0588

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.0429

Gnomad4 FIN

AF:

0.0437

Gnomad4 NFE

AF:

0.0397

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0369

Hom.:

169

Bravo

AF:

0.0275

TwinsUK

AF:

0.0434

AC:

161

ALSPAC

AF:

0.0353

AC:

136

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.0391

AC:

336

ExAC

AF:

0.0343

AC:

4159

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.0389

EpiControl

AF:

0.0385

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - variant associated with prostate cancer. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Combined oxidative phosphorylation defect type 17

Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	Feb 02, 2022	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely benign. Following criteria are met: 0308 - Population frequency for this variant is out of keeping with known incidence of autosomal recessive Combined oxidative phosphorylation deficiency 17 (MIM#615440). (SB) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 15, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Prostate cancer, hereditary, 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2002

- -

Prostate cancer, hereditary, 2;C3809526:Combined oxidative phosphorylation defect type 17

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.051

T;.;.

Eigen

Benign

-0.081

Eigen_PC

Benign

0.0043

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.92

D;D;D

MetaRNN

Benign

0.0092

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.0

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.34

B;B;.

Vest4

0.29

MPC

0.23

ClinPred

0.043

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.55

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