Variant 17-13011692-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018127.7(ELAC2):c.650C>G(p.Ser217Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S217L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ELAC2
NM_018127.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.72

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17411664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC2	NM_018127.7 linkuse as main transcript	c.650C>G	p.Ser217Trp	missense_variant	7/24	ENST00000338034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC2	ENST00000338034.9 linkuse as main transcript	c.650C>G	p.Ser217Trp	missense_variant	7/24	1	NM_018127.7	P2	Q9BQ52-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74094

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Benign

-0.16

Cadd

Benign

Dann

Benign

0.37

DEOGEN2

Benign

0.12

T;.;T;T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.4

M;.;.;.;.

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-1.3

N;N;.;.;.

REVEL

Benign

0.21

Sift

Uncertain

0.026

D;D;.;.;.

Sift4G

Uncertain

0.045

D;D;.;.;.

Polyphen

0.99

D;D;.;.;.

Vest4

0.47

MutPred

0.20

Loss of phosphorylation at S217 (P = 0.0048);.;.;.;.;

MVP

0.90

MPC

0.77

ClinPred

0.70

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over