Submissions for variant NM_003647.3(DGKE):c.966G>A (p.Trp322Ter)

gnomAD frequency: 0.00016  dbSNP: rs138924661

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Precision Medicine, Vanderbilt University Medical Center	RCV000760165	SCV000889982	pathogenic	Immunoglobulin-mediated membranoproliferative glomerulonephritis	2018-03-16	criteria provided, single submitter	research
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000760165	SCV001368100	pathogenic	Immunoglobulin-mediated membranoproliferative glomerulonephritis	2019-06-12	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2.
Invitae	RCV001854681	SCV002234882	pathogenic	not provided	2023-12-07	criteria provided, single submitter	clinical testing	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000122617	SCV002587670	pathogenic	Atypical hemolytic-uremic syndrome	2020-04-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000760165	SCV002810357	pathogenic	Immunoglobulin-mediated membranoproliferative glomerulonephritis	2022-04-07	criteria provided, single submitter	clinical testing
OMIM	RCV000043567	SCV000071437	risk factor	Hemolytic uremic syndrome, atypical, susceptibility to, 7	2013-05-01	no assertion criteria provided	literature only
Richard Lifton Laboratory, Yale University School of Medicine	RCV000122617	SCV000155124	probable-pathogenic	Atypical hemolytic-uremic syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.