Variant 1-204137209-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018208.4(ETNK2):c.909G>C(p.Glu303Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,613,956 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 12 hom. )

Consequence

ETNK2
NM_018208.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.552

Variant links:

Genes affected

ETNK2 (HGNC:25575): (ethanolamine kinase 2) The protein encoded by this gene is a member of choline/ethanolamine kinase family which catalyzes the first step of phosphatidylethanolamine (PtdEtn) biosynthesis via the cytidine diphosphate (CDP) ethanolamine pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ETNK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00886035).

BP6

Variant 1-204137209-C-G is Benign according to our data. Variant chr1-204137209-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639824.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETNK2	NM_018208.4 linkuse as main transcript	c.909G>C	p.Glu303Asp	missense_variant	6/8	ENST00000367202.9	NP_060678.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9 linkuse as main transcript	c.909G>C	p.Glu303Asp	missense_variant	6/8	1	NM_018208.4	ENSP00000356170	P1	Q9NVF9-1

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

421

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00463

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00273

AC:

684

AN:

250970

Hom.:

AF XY:

0.00272

AC XY:

369

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00601

Gnomad NFE exome

AF:

0.00423

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00265

AC:

3868

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

1938

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00596

Gnomad4 NFE exome

AF:

0.00295

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00276

AC:

421

AN:

152326

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00650

Gnomad4 NFE

AF:

0.00463

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00384

Hom.:

Bravo

AF:

0.00173

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00315

AC:

383

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00420

EpiControl

AF:

0.00380

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ETNK2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;T;T;T

Eigen

Benign

0.013

Eigen_PC

Benign

0.049

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.0089

T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.5

L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.2

N;N;N;D

REVEL

Benign

0.098

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.18

T;T;.;.

Polyphen

0.096

B;B;.;.

Vest4

0.37

MutPred

0.48

Gain of catalytic residue at E303 (P = 0.2117);Gain of catalytic residue at E303 (P = 0.2117);.;.;

MVP

0.58

MPC

0.28

ClinPred

0.035

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.36

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