17-56834878-G-A

Position:

• chr17-56834878-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003647.3(DGKE):​c.83G>A​(p.Cys28Tyr) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DGKE NM_003647.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89

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]

C17orf67 (HGNC:27900): (chromosome 17 open reading frame 67) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2800933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKE	NM_003647.3	c.83G>A	p.Cys28Tyr	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.83G>A	p.Cys28Tyr	missense_variant	2/12	1	NM_003647.3	ENSP00000284061	P1
DGKE	ENST00000572810.1	c.83G>A	p.Cys28Tyr	missense_variant	2/2	1		ENSP00000459295
DGKE	ENST00000576869.5	n.231G>A		non_coding_transcript_exon_variant	2/6	1
C17orf67	ENST00000487705.1	n.285+3611C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 22, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with DGKE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 28 of the DGKE protein (p.Cys28Tyr). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.058
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.83	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.99	N;.
REVEL	Benign	0.091
Sift	Benign	0.042	D;.
Sift4G	Benign	0.67	T;T
Polyphen		0.11	B;.
Vest4		0.48
MutPred		0.47		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.59
MPC		0.65
ClinPred		0.72	D
GERP RS		4.5
Varity_R		0.31
gMVP		0.61

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: chr17-54912239;