chr17-56834856-C-CACCT

Variant names:

• chr17-56834856-C-CACCT
• rs1214440741
• NM_003647.3:c.62_65dupACCT

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.62_65dupACCT​(p.Ile23ProfsTer20) variant causes a frameshift 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L22L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DGKE NM_003647.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.29
• Publications: 0 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 50 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-56834856-C-CACCT is Pathogenic according to our data. Variant chr17-56834856-C-CACCT is described in ClinVar as Pathogenic. ClinVar VariationId is 1179079.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	NM_003647.3	MANE Select	c.62_65dupACCT	p.Ile23ProfsTer20	frameshift	Exon 2 of 12	NP_003638.1	A1L4Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	ENST00000284061.8	TSL:1 MANE Select	c.62_65dupACCT	p.Ile23ProfsTer20	frameshift	Exon 2 of 12	ENSP00000284061.3	P52429-1
	DGKE	ENST00000572810.1	TSL:1	c.62_65dupACCT	p.Ile23ProfsTer20	frameshift	Exon 2 of 2	ENSP00000459295.1	P52429-2
	DGKE	ENST00000576869.5	TSL:1	n.210_213dupACCT		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248412 AF XY: 0.00

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Immunoglobulin-mediated membranoproliferative glomerulonephritis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=5/195	disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1214440741; hg19: chr17-54912217;