17-56835096-A-T

Variant summary

Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3_ModeratePP5

The NM_003647.3(DGKE):​c.301A>T​(p.Lys101*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

DGKE
NM_003647.3 stop_gained

Scores

4
1
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.19
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 13 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 17-56835096-A-T is Pathogenic according to our data. Variant chr17-56835096-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 446215.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DGKENM_003647.3 linkc.301A>T p.Lys101* stop_gained Exon 2 of 12 ENST00000284061.8 NP_003638.1 P52429-1A1L4Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DGKEENST00000284061.8 linkc.301A>T p.Lys101* stop_gained Exon 2 of 12 1 NM_003647.3 ENSP00000284061.3 P52429-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Atypical hemolytic-uremic syndrome Pathogenic:1
Feb 07, 2014
Yale Center for Mendelian Genomics, Yale University
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
42
DANN
Uncertain
0.99
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Benign
0.60
D
Vest4
0.18
GERP RS
4.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.83
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.83
Position offset: -2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777787526; hg19: chr17-54912457; API