Genetic Variant NM_018208.4:c.311A>G (chr1-204149910-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018208.4(ETNK2):c.311A>G(p.Asp104Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000271 in 1,440,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ETNK2
NM_018208.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10191363).

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.311A>G	p.Asp104Gly	missense	Exon 2 of 8	NP_060678.2	Q9NVF9-1
ETNK2	NM_001297760.2		c.311A>G	p.Asp104Gly	missense	Exon 2 of 8	NP_001284689.1	Q9NVF9-2
ETNK2	NM_001297762.2		c.311A>G	p.Asp104Gly	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.311A>G	p.Asp104Gly	missense	Exon 2 of 8	ENSP00000356170.4	Q9NVF9-1
ETNK2	ENST00000367201.7	TSL:2	c.311A>G	p.Asp104Gly	missense	Exon 2 of 8	ENSP00000356169.3	Q9NVF9-2
ETNK2	ENST00000429525.1	TSL:4	c.-2A>G		5_prime_UTR	Exon 3 of 3	ENSP00000394618.1	B7ZC35

Frequencies

GnomAD3 genomes

AF:

0.0000148

AC:

AN:

135148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000278

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:

0.0000154

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

179998

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1305760

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

644804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28872

American (AMR)

AF:

0.00

AC:

AN:

34664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21050

East Asian (EAS)

AF:

0.00

AC:

AN:

26786

South Asian (SAS)

AF:

0.00

AC:

AN:

79562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5150

European-Non Finnish (NFE)

AF:

0.0000354

AC:

AN:

1017560

Other (OTH)

AF:

0.0000196

AC:

AN:

51102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.0000148

AC:

AN:

135148

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

64360

show subpopulations

African (AFR)

AF:

0.0000278

AC:

AN:

35936

American (AMR)

AF:

0.00

AC:

AN:

11644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3380

East Asian (EAS)

AF:

0.00

AC:

AN:

4212

South Asian (SAS)

AF:

0.00

AC:

AN:

4126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

65122

Other (OTH)

AF:

0.00

AC:

AN:

1876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000658

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.035

Eigen

Benign

-0.18

Eigen_PC

Benign

0.0059

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.75

M_CAP

Benign

0.0050

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.3

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.6

REVEL

Benign

0.10

Sift

Benign

0.31

Sift4G

Benign

0.41

Polyphen

0.0040

Vest4

0.19

MVP

0.61

MPC

0.37

ClinPred

0.37

GERP RS

5.5

PromoterAI

-0.053

Neutral

(source)

Varity_R

0.22

gMVP

0.62

Mutation Taster

=78/22

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