rs17552022

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018127.7(ELAC2):c.1893A>G(p.Thr631Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,614,118 control chromosomes in the GnomAD database, including 11,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 797 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10762 hom. )

Consequence

ELAC2
NM_018127.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.55

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation defect type 17
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ELAC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-12994978-T-C is Benign according to our data. Variant chr17-12994978-T-C is described in ClinVar as Benign. ClinVar VariationId is 380022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAC2	NM_018127.7 link	c.1893A>G	p.Thr631Thr	synonymous_variant	Exon 20 of 24	ENST00000338034.9	NP_060597.4	Q9BQ52-1A0A0S2Z5M8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9 link	c.1893A>G	p.Thr631Thr	synonymous_variant	Exon 20 of 24	1	NM_018127.7	ENSP00000337445.4		Q9BQ52-1

Frequencies

GnomAD3 genomes

AF:

0.0866

AC:

13173

AN:

152160

Hom.:

796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.0766

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0975

Gnomad FIN

AF:

0.0824

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.110

GnomAD2 exomes

AF:

0.0987

AC:

24819

AN:

251480

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.0593

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.0797

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.116

AC:

169034

AN:

1461840

Hom.:

10762

Cov.:

AF XY:

0.117

AC XY:

85164

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0218

AC:

729

AN:

33480

American (AMR)

AF:

0.0623

AC:

2788

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

4974

AN:

26136

East Asian (EAS)

AF:

0.000453

AC:

AN:

39700

South Asian (SAS)

AF:

0.117

AC:

10110

AN:

86258

European-Finnish (FIN)

AF:

0.0823

AC:

4396

AN:

53384

Middle Eastern (MID)

AF:

0.205

AC:

1183

AN:

5768

European-Non Finnish (NFE)

AF:

0.124

AC:

137746

AN:

1111994

Other (OTH)

AF:

0.117

AC:

7090

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

9931

19862

29793

39724

49655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4820

9640

14460

19280

24100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0865

AC:

13169

AN:

152278

Hom.:

797

Cov.:

AF XY:

0.0846

AC XY:

6300

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0215

AC:

896

AN:

41580

American (AMR)

AF:

0.0764

AC:

1169

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

677

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0976

AC:

471

AN:

4826

European-Finnish (FIN)

AF:

0.0824

AC:

874

AN:

10612

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8546

AN:

68000

Other (OTH)

AF:

0.109

AC:

229

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

602

1204

1807

2409

3011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

1877

Bravo

AF:

0.0843

Asia WGS

AF:

0.0390

AC:

138

AN:

3478

EpiCase

AF:

0.134

EpiControl

AF:

0.140

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation defect type 17

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 25, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 16, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Prostate cancer, hereditary, 2

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.095

(source)

DANN

Benign

0.49

PhyloP100

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over