rs312262694

Positions:

• chr17-56834983-G-C

Variant summary

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

The NM_003647.3(DGKE):​c.188G>C​(p.Arg63Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DGKE NM_003647.3 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 0.883

Genes affected

DGKE (HGNC:2852): (diacylglycerol kinase epsilon) Diacylglycerol kinases are thought to be involved mainly in the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. When expressed in mammalian cells, DGK-epsilon shows specificity for arachidonyl-containing diacylglycerol. DGK-epsilon is expressed predominantly in testis. [provided by RefSeq, Jul 2008]

DGKE (HGNC:):

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/exons	MANE	Protein	UniProt
DGKE	NM_003647.3	c.188G>C	p.Arg63Pro	missense_variant	2/12	ENST00000284061.8	NP_003638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKE	ENST00000284061.8	c.188G>C	p.Arg63Pro	missense_variant	2/12	1	NM_003647.3	ENSP00000284061.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

AHUS, SUSCEPTIBILITY TO, 7 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Uncertain	0.67	D;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.1	N;.
REVEL	Uncertain	0.63
Sift	Benign	0.20	T;.
Sift4G	Benign	0.20	T;T
Polyphen		0.096	B;.
Vest4		0.51
MutPred		0.65		Loss of MoRF binding (P = 0.003);Loss of MoRF binding (P = 0.003);
MVP		0.86
MPC		0.84
ClinPred		0.64	D
GERP RS		-0.55
Varity_R		0.91
gMVP		0.79

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

LitVar

Other links and lift over

dbSNP: rs312262694; hg19: chr17-54912344;