rs374386002

Variant names:

• chr1-204149961-C-A
• rs374386002
• NM_018208.4:c.260G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204149961-C-A
• chr1-204149961-C-G
• chr1-204149961-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018208.4(ETNK2):​c.260G>T​(p.Arg87Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R87H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ETNK2 NM_018208.4 missense, splice_region
• Scores: Splicing: ADA: 0.001528
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24

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]

ACMG classification

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=0.099772334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETNK2	NM_018208.4	c.260G>T	p.Arg87Leu	missense_variant, splice_region_variant	Exon 2 of 8	ENST00000367202.9	NP_060678.2
ETNK2	NM_001297760.2	c.260G>T	p.Arg87Leu	missense_variant, splice_region_variant	Exon 2 of 8		NP_001284689.1
ETNK2	NM_001297762.2	c.260G>T	p.Arg87Leu	missense_variant, splice_region_variant	Exon 2 of 7		NP_001284691.1
ETNK2	NM_001297761.2	c.-17+1634G>T		intron_variant	Intron 1 of 6		NP_001284690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9	c.260G>T	p.Arg87Leu	missense_variant, splice_region_variant	Exon 2 of 8	1	NM_018208.4	ENSP00000356170.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.019	.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.67	N;N
REVEL	Benign	0.057
Sift	Benign	0.71	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.0050	B;B
Vest4		0.30
MutPred		0.65		Loss of MoRF binding (P = 0.0256);Loss of MoRF binding (P = 0.0256);
MVP		0.56
MPC		0.35
ClinPred		0.79	D
GERP RS		4.6
Varity_R		0.097
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0015
dbscSNV1_RF	Benign	0.054
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

Other links and lift over

dbSNP: rs374386002; hg19: chr1-204119089;