Variant chr1-204141455-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018208.4(ETNK2):c.644T>C(p.Leu215Pro) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ETNK2
NM_018208.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

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:

ERLNC1 (HGNC:41109): (estrogen receptor responsive lncRNA 1)

ERLNC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETNK2	NM_018208.4 linkuse as main transcript	c.644T>C	p.Leu215Pro	missense_variant, splice_region_variant	4/8	ENST00000367202.9
ERLNC1	NR_123739.1 linkuse as main transcript	n.48A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETNK2	ENST00000367202.9 linkuse as main transcript	c.644T>C	p.Leu215Pro	missense_variant, splice_region_variant	4/8	1	NM_018208.4	P1	Q9NVF9-1
ERLNC1	ENST00000658822.1 linkuse as main transcript	n.52A>G		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.99e-7

AC:

AN:

1431054

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708924

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.12e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.644T>C (p.L215P) alteration is located in exon 4 (coding exon 4) of the ETNK2 gene. This alteration results from a T to C substitution at nucleotide position 644, causing the leucine (L) at amino acid position 215 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.079

.;T;T;T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.47

T;T;T;T;T

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.72

D;D;D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.9

L;L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.7

D;D;D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.16

T;T;T;T;D

Sift4G

Benign

0.10

T;T;.;.;.

Polyphen

1.0

D;D;.;.;.

Vest4

0.25

MutPred

0.66

Gain of disorder (P = 0.0056);Gain of disorder (P = 0.0056);.;.;.;

MVP

0.89

MPC

1.2

ClinPred

0.96

GERP RS

5.9

Varity_R

0.64

gMVP

0.86

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over