1-204141455-A-G

Variant summary

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

The NM_018208.4(ETNK2):ā€‹c.644T>Cā€‹(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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.0e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ETNK2
NM_018208.4 missense, splice_region

Scores

1
8
10

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

Genome browser will be placed here

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
ETNK2NM_018208.4 linkuse as main transcriptc.644T>C p.Leu215Pro missense_variant, splice_region_variant 4/8 ENST00000367202.9
ERLNC1NR_123739.1 linkuse as main transcriptn.48A>G non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ETNK2ENST00000367202.9 linkuse as main transcriptc.644T>C p.Leu215Pro missense_variant, splice_region_variant 4/81 NM_018208.4 P1Q9NVF9-1
ERLNC1ENST00000658822.1 linkuse as main transcriptn.52A>G non_coding_transcript_exon_variant 1/2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.99e-7
AC:
1
AN:
1431054
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
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.:
33

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 submitterclinical testingAmbry GeneticsNov 14, 2023The 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
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
26
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
D
LIST_S2
Benign
0.47
T;T;T;T;T
M_CAP
Benign
0.061
D
MetaRNN
Uncertain
0.72
D;D;D;D;D
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
1.9
L;L;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.53
T
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
D
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.

Other links and lift over

hg19: chr1-204110583; API