Variant 17-56834924-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003647.3(DGKE):c.129G>A(p.Gln43Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,613,600 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 8 hom. )

Consequence

DGKE
NM_003647.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.45

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]

DGKE links:

C17orf67 (HGNC:27900): (chromosome 17 open reading frame 67) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

C17orf67 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-56834924-G-A is Benign according to our data. Variant chr17-56834924-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 731569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-56834924-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=3.45 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00198 (302/152342) while in subpopulation AMR AF= 0.00314 (48/15306). AF 95% confidence interval is 0.00252. There are 0 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKE	NM_003647.3 link	c.129G>A	p.Gln43Gln	synonymous_variant	2/12	ENST00000284061.8	NP_003638.1	P52429-1A1L4Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKE	ENST00000284061.8 link	c.129G>A	p.Gln43Gln	synonymous_variant	2/12	1	NM_003647.3	ENSP00000284061.3		P52429-1

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00196

AC:

490

AN:

249552

Hom.:

AF XY:

0.00181

AC XY:

244

AN XY:

135166

show subpopulations

Gnomad AFR exome

AF:

0.000374

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00202

Gnomad NFE exome

AF:

0.00315

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00219

AC:

3201

AN:

1461258

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

1511

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00263

Gnomad4 NFE exome

AF:

0.00256

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152342

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00285

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.00209

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00261

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	DGKE: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Immunoglobulin-mediated membranoproliferative glomerulonephritis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.95

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over