rs138924661
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003647.3(DGKE):c.966G>A(p.Trp322*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,614,056 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003647.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DGKE | ENST00000284061.8 | c.966G>A | p.Trp322* | stop_gained | Exon 6 of 12 | 1 | NM_003647.3 | ENSP00000284061.3 | ||
DGKE | ENST00000572944.1 | c.795G>A | p.Trp265* | stop_gained | Exon 5 of 10 | 1 | ENSP00000458493.1 | |||
TRIM25 | ENST00000648772.1 | n.*313+3170C>T | intron_variant | Intron 10 of 12 | ENSP00000498158.1 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251454Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135894
GnomAD4 exome AF: 0.000187 AC: 273AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 117AN XY: 727228
GnomAD4 genome AF: 0.000151 AC: 23AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74354
ClinVar
Submissions by phenotype
Immunoglobulin-mediated membranoproliferative glomerulonephritis Pathogenic:3
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2. -
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not provided Pathogenic:2
This sequence change creates a premature translational stop signal (p.Trp322*) in the DGKE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DGKE are known to be pathogenic (PMID: 23274426, 23542698). This variant is present in population databases (rs138924661, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with nephrotic syndrome and atypical hemolytic uremic syndrome (PMID: 23542698, 25135762, 25854283, 28496993). ClinVar contains an entry for this variant (Variation ID: 135641). For these reasons, this variant has been classified as Pathogenic. -
PP1, PM3_very_strong, PS4_moderate, PVS1 -
Atypical hemolytic-uremic syndrome Pathogenic:2
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Hemolytic uremic syndrome, atypical, susceptibility to, 7 Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at