Genetic Variant ETNK2:p.Val109Leu (chr1-204149896-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018208.4(ETNK2):c.325G>T(p.Val109Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000019 in 1,579,046 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V109M) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ETNK2
NM_018208.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.51

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETNK2	NM_018208.4	MANE Select	c.325G>T	p.Val109Leu	missense	Exon 2 of 8	NP_060678.2	Q9NVF9-1
ETNK2	NM_001297760.2		c.325G>T	p.Val109Leu	missense	Exon 2 of 8	NP_001284689.1	Q9NVF9-2
ETNK2	NM_001297762.2		c.325G>T	p.Val109Leu	missense	Exon 2 of 7	NP_001284691.1	Q9NVF9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETNK2	ENST00000367202.9	TSL:1 MANE Select	c.325G>T	p.Val109Leu	missense	Exon 2 of 8	ENSP00000356170.4	Q9NVF9-1
ETNK2	ENST00000367201.7	TSL:2	c.325G>T	p.Val109Leu	missense	Exon 2 of 8	ENSP00000356169.3	Q9NVF9-2
ETNK2	ENST00000429525.1	TSL:4	c.13G>T	p.Val5Leu	missense	Exon 3 of 3	ENSP00000394618.1	B7ZC35

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151840

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00000515

AC:

AN:

194356

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1427206

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706670

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32548

American (AMR)

AF:

0.00

AC:

AN:

39606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25514

East Asian (EAS)

AF:

0.00

AC:

AN:

37508

South Asian (SAS)

AF:

0.00

AC:

AN:

81342

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1094788

Other (OTH)

AF:

0.00

AC:

AN:

59136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000659

AC:

AN:

151840

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74142

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41332

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67962

Other (OTH)

AF:

0.000478

AC:

AN:

2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

0.062

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.6

PhyloP100

4.5

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

REVEL

Benign

0.27

Sift

Benign

0.15

Sift4G

Benign

0.097

Polyphen

0.044

Vest4

0.53

MutPred

0.72

Gain of sheet (P = 0.0827)

MVP

0.45

MPC

0.38

ClinPred

0.63

GERP RS

4.6

PromoterAI

0.027

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.42

gMVP

0.76

Mutation Taster

=53/47

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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