Variant X-50380018-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001013742.4(DGKK):c.2717G>A(p.Arg906His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,210,065 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 109 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.00024 ( 0 hom. 101 hem. )

Consequence

DGKK
NM_001013742.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

DGKK (HGNC:32395): (diacylglycerol kinase kappa) The protein encoded by this gene is an enzyme that phosphorylates diacylglycerol, converting it to phosphatidic acid. The encoded protein is a membrane protein and is inhibited by hydrogen peroxide. Variations in this gene have been associated with hypospadias. [provided by RefSeq, Mar 2011]

DGKK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005242914).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKK	NM_001013742.4 linkuse as main transcript	c.2717G>A	p.Arg906His	missense_variant	19/28	ENST00000611977.2	NP_001013764.1	Q5KSL6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKK	ENST00000611977.2 linkuse as main transcript	c.2717G>A	p.Arg906His	missense_variant	19/28	1	NM_001013742.4	ENSP00000477515.1		Q5KSL6

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

112116

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

AN XY:

34284

show subpopulations

Gnomad AFR

AF:

0.000227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00225

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.000662

GnomAD3 exomes

AF:

0.000563

AC:

102

AN:

181180

Hom.:

AF XY:

0.000594

AC XY:

AN XY:

67334

show subpopulations

Gnomad AFR exome

AF:

0.000161

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00207

Gnomad SAS exome

AF:

0.00184

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000674

GnomAD4 exome

AF:

0.000243

AC:

267

AN:

1097892

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

101

AN XY:

363362

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000682

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00139

Gnomad4 SAS exome

AF:

0.00185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000891

Gnomad4 OTH exome

AF:

0.000521

GnomAD4 genome

AF:

0.000250

AC:

AN:

112173

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

AN XY:

34351

show subpopulations

Gnomad4 AFR

AF:

0.000226

Gnomad4 AMR

AF:

0.000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00225

Gnomad4 SAS

AF:

0.00114

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.000654

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.000637

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.2717G>A (p.R906H) alteration is located in exon 19 (coding exon 19) of the DGKK gene. This alteration results from a G to A substitution at nucleotide position 2717, causing the arginine (R) at amino acid position 906 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.050

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0052

PrimateAI

Benign

0.36

Sift4G

Pathogenic

0.0010

Polyphen

0.13

Vest4

0.062

MVP

0.21

GERP RS

2.5

Varity_R

0.085

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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