NM_018127.7:c.1560A>G

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.1560A>G(p.Thr520Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,613,436 control chromosomes in the GnomAD database, including 69,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T520T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.27 ( 5692 hom., cov: 32)

Exomes 𝑓: 0.29 ( 63634 hom. )

Consequence

ELAC2
NM_018127.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.71

Publications

21 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=-0.68).

BP6

Variant 17-12996646-T-C is Benign according to our data. Variant chr17-12996646-T-C is described in ClinVar as Benign. ClinVar VariationId is 379971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAC2	NM_018127.7 link	c.1560A>G	p.Thr520Thr	synonymous_variant	Exon 17 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.1560A>G	p.Thr520Thr	synonymous_variant	Exon 17 of 24	1	NM_018127.7	ENSP00000337445.4		Q9BQ52-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40637

AN:

151840

Hom.:

5682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.0301

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.330

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.275

GnomAD2 exomes

AF:

0.272

AC:

68113

AN:

250592

AF XY:

0.276

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.367

Gnomad EAS exome

AF:

0.0342

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

AF:

0.290

AC:

423972

AN:

1461478

Hom.:

63634

Cov.:

AF XY:

0.291

AC XY:

211294

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.223

AC:

7477

AN:

33478

American (AMR)

AF:

0.256

AC:

11440

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

9714

AN:

26128

East Asian (EAS)

AF:

0.0311

AC:

1235

AN:

39698

South Asian (SAS)

AF:

0.285

AC:

24612

AN:

86248

European-Finnish (FIN)

AF:

0.316

AC:

16849

AN:

53266

Middle Eastern (MID)

AF:

0.340

AC:

1958

AN:

5766

European-Non Finnish (NFE)

AF:

0.300

AC:

333434

AN:

1111836

Other (OTH)

AF:

0.286

AC:

17253

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19271

38542

57814

77085

96356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10838

21676

32514

43352

54190

<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:

0.268

AC:

40663

AN:

151958

Hom.:

5692

Cov.:

AF XY:

0.266

AC XY:

19738

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.222

AC:

9211

AN:

41462

American (AMR)

AF:

0.252

AC:

3845

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1317

AN:

3470

East Asian (EAS)

AF:

0.0300

AC:

154

AN:

5140

South Asian (SAS)

AF:

0.269

AC:

1292

AN:

4804

European-Finnish (FIN)

AF:

0.312

AC:

3291

AN:

10552

Middle Eastern (MID)

AF:

0.331

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.302

AC:

20505

AN:

67954

Other (OTH)

AF:

0.272

AC:

572

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1523

3046

4570

6093

7616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.264

Hom.:

1767

Bravo

AF:

0.260

Asia WGS

AF:

0.141

AC:

494

AN:

3478

EpiCase

AF:

0.303

EpiControl

AF:

0.298

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 15, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Dec 02, 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

-0.68

CADD

Benign

0.12

(source)

DANN

Benign

0.61

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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