rs4792311

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_018127.7(ELAC2):c.650C>T(p.Ser217Leu) variant causes a missense change. The variant allele was found at a frequency of 0.289 in 1,613,650 control chromosomes in the GnomAD database, including 69,746 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. S217S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.27 ( 5876 hom., cov: 32)

Exomes 𝑓: 0.29 ( 63870 hom. )

Consequence

ELAC2
NM_018127.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:9

Conservation

PhyloP100: 3.72

Publications

102 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet
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 -16 ACMG points.

BP6

Variant 17-13011692-G-A is Benign according to our data. Variant chr17-13011692-G-A is described in ClinVar as Benign. ClinVar VariationId is 5055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018127.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELAC2	NM_018127.7	MANE Select	c.650C>T	p.Ser217Leu	missense	Exon 7 of 24	NP_060597.4
ELAC2	NM_173717.2		c.650C>T	p.Ser217Leu	missense	Exon 7 of 24	NP_776065.1
ELAC2	NM_001165962.2		c.560-1021C>T		intron	N/A	NP_001159434.1	Q9BQ52-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.650C>T	p.Ser217Leu	missense	Exon 7 of 24	ENSP00000337445.4	Q9BQ52-1
ELAC2	ENST00000923774.1		c.752C>T	p.Ser251Leu	missense	Exon 8 of 25	ENSP00000593833.1
ELAC2	ENST00000860253.1		c.650C>T	p.Ser217Leu	missense	Exon 7 of 25	ENSP00000530312.1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41571

AN:

151738

Hom.:

5873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.0301

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.285

GnomAD2 exomes

AF:

0.274

AC:

68792

AN:

251474

AF XY:

0.277

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.367

Gnomad EAS exome

AF:

0.0348

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.291

AC:

424894

AN:

1461794

Hom.:

63870

Cov.:

AF XY:

0.291

AC XY:

211680

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.244

AC:

8181

AN:

33480

American (AMR)

AF:

0.259

AC:

11566

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

9726

AN:

26134

East Asian (EAS)

AF:

0.0318

AC:

1263

AN:

39700

South Asian (SAS)

AF:

0.285

AC:

24582

AN:

86252

European-Finnish (FIN)

AF:

0.316

AC:

16904

AN:

53420

Middle Eastern (MID)

AF:

0.343

AC:

1980

AN:

5768

European-Non Finnish (NFE)

AF:

0.300

AC:

333349

AN:

1111922

Other (OTH)

AF:

0.287

AC:

17343

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

18375

36751

55126

73502

91877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10836

21672

32508

43344

54180

<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:

0.274

AC:

41587

AN:

151856

Hom.:

5876

Cov.:

AF XY:

0.272

AC XY:

20195

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.242

AC:

10031

AN:

41402

American (AMR)

AF:

0.257

AC:

3917

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1316

AN:

3468

East Asian (EAS)

AF:

0.0299

AC:

154

AN:

5146

South Asian (SAS)

AF:

0.268

AC:

1291

AN:

4810

European-Finnish (FIN)

AF:

0.313

AC:

3287

AN:

10516

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.302

AC:

20519

AN:

67940

Other (OTH)

AF:

0.281

AC:

593

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1546

3092

4637

6183

7729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.284

Hom.:

23880

Bravo

AF:

0.267

TwinsUK

AF:

0.299

AC:

1110

ALSPAC

AF:

0.301

AC:

1161

ESP6500AA

AF:

0.235

AC:

1034

ESP6500EA

AF:

0.297

AC:

2552

ExAC

AF:

0.271

AC:

32907

Asia WGS

AF:

0.141

AC:

493

AN:

3478

EpiCase

AF:

0.302

EpiControl

AF:

0.298

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined oxidative phosphorylation defect type 17 (5)

not provided (2)

not specified (1)

Prostate cancer, hereditary, 2 (1)

Prostate cancer, hereditary, 2;C3809526:Combined oxidative phosphorylation defect type 17 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.018

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

3.7

PROVEAN

Benign

-0.67

REVEL

Benign

0.15

Sift

Benign

0.32

Sift4G

Benign

0.39

Polyphen

0.36

Vest4

0.10

MPC

0.22

ClinPred

0.013

GERP RS

3.2

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.027

gMVP

0.43

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.25

Position offset: -29

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over