1-204141455-A-G

Variant names:

• chr1-204141455-A-G
• NM_018208.4:c.644T>C

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89

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)

ACMG classification

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 rank	MANE	Protein	UniProt
ETNK2	NM_018208.4	c.644T>C	p.Leu215Pro	missense_variant, splice_region_variant	Exon 4 of 8	ENST00000367202.9	NP_060678.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9	c.644T>C	p.Leu215Pro	missense_variant, splice_region_variant	Exon 4 of 8	1	NM_018208.4	ENSP00000356170.4

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

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

Submissions by phenotype

not specified Uncertain:1

Nov 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	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;.;.;.
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;