17-56834827-C-A

Variant names:

• chr17-56834827-C-A
• rs148605410
• NM_003647.3:c.32C>A

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_003647.3(DGKE):​c.32C>A​(p.Ser11*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic,low penetrance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: DGKE NM_003647.3 stop_gained
• Clinical Significance: Pathogenic, low penetrance criteria provided, single submitter P:2 O:1
• Conservation: PhyloP100: 1.69
• Publications: 5 publications found

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

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 49 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-56834827-C-A is Pathogenic according to our data. Variant chr17-56834827-C-A is described in ClinVar as Pathogenic,_low_penetrance. ClinVar VariationId is 50789.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003647.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	NM_003647.3	MANE Select	c.32C>A	p.Ser11*	stop_gained	Exon 2 of 12	NP_003638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	ENST00000284061.8	TSL:1 MANE Select	c.32C>A	p.Ser11*	stop_gained	Exon 2 of 12	ENSP00000284061.3
	DGKE	ENST00000572810.1	TSL:1	c.32C>A	p.Ser11*	stop_gained	Exon 2 of 2	ENSP00000459295.1
	DGKE	ENST00000576869.5	TSL:1	n.180C>A		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1455156 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 723396

African (AFR) AF: 0.0000300 AC: 1 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25888

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4648

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1109616

Other (OTH) AF: 0.00 AC: 0 AN: 60026

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic, low penetrance

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atypical hemolytic-uremic syndrome Pathogenic:2

Richard Lifton Laboratory, Yale University School of Medicine

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Sep 26, 2025

Genomenon, Inc, Genomenon, Inc

Significance: Pathogenic, low penetrance

Review Status: criteria provided, single submitter

Collection Method: curation

DGKE p.Ser11Ter (c.32C>A) is a nonsense variant that introduces a premature stop codon at amino acid position 11, creating a truncated protein that may be subject to nonsense-mediated mRNA decay. This variant has been observed in at least one proband affected with atypical hemolytic-uremic syndrome (PMID:23542698). It is absent or not present at a significant frequency in gnomAD. In conclusion, we classify DGKE p.Ser11Ter (c.32C>A) as a pathogenic, low penetrance variant.

Hemolytic uremic syndrome, atypical, susceptibility to, 7 Other:1

May 01, 2013

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	34
DANN	Uncertain	0.98
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.069
FATHMM_MKL	Benign	0.25	N
PhyloP100		1.7
Vest4		0.17
GERP RS		2.3
PromoterAI		0.029	Neutral
Mutation Taster		=11/189	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs148605410; hg19: chr17-54912188; COSMIC: COSV52349508; COSMIC: COSV52349508;