17-56834854-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003647.3(DGKE):c.59G>A(p.Gly20Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,612,018 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (31 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (39 hom.)
• Consequence: DGKE NM_003647.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.65

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024999678).
• BP6: Variant 17-56834854-G-A is Benign according to our data. Variant chr17-56834854-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 783790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-56834854-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1971/152362) while in subpopulation AFR AF= 0.0448 (1862/41578). AF 95% confidence interval is 0.0431. There are 31 homozygotes in gnomad4. There are 949 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKE	NM_003647.3	c.59G>A	p.Gly20Glu	missense_variant	2/12	ENST00000284061.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKE	ENST00000284061.8	c.59G>A	p.Gly20Glu	missense_variant	2/12	1	NM_003647.3	P1
DGKE	ENST00000572810.1	c.59G>A	p.Gly20Glu	missense_variant	2/2	1
DGKE	ENST00000576869.5	n.207G>A		non_coding_transcript_exon_variant	2/6	1
C17orf67	ENST00000487705.1	n.285+3635C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1964 AN: 152244 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00337 AC: 838 AN: 248394 Hom.: 23 AF XY: 0.00250 AC XY: 337 AN XY: 134674

Gnomad AFR exome AF: 0.0469

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000357

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00121 AC: 1773 AN: 1459656 Hom.: 39 Cov.: 31 AF XY: 0.00102 AC XY: 744 AN XY: 725932

Gnomad4 AFR exome AF: 0.0437

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000396

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.0129 AC: 1971 AN: 152362 Hom.: 31 Cov.: 33 AF XY: 0.0127 AC XY: 949 AN XY: 74506

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00626 Hom.: 7

Bravo AF: 0.0149

ESP6500AA AF: 0.0390 AC: 172

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00421 AC: 511

Asia WGS AF: 0.00260 AC: 9 AN: 3476

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 14, 2020	This variant is associated with the following publications: (PMID: 29440240) -

Kidney disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.65	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N;N
MutationTaster	Benign	0.91	N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.97	N;.
REVEL	Benign	0.047
Sift	Benign	0.26	T;.
Sift4G	Benign	0.51	T;T
Polyphen		0.0	B;.
Vest4		0.17
MVP		0.56
MPC		0.47
ClinPred		0.017	T
GERP RS		3.3
Varity_R		0.090
gMVP		0.56

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: rs73994915; hg19: chr17-54912215;