Genetic Variant DGKK:c.2118+8C>T (chrX-50387546-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001013742.4(DGKK):c.2118+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,182,573 control chromosomes in the GnomAD database, including 26,745 homozygotes. There are 89,746 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 3324 hom., 8727 hem., cov: 23)

Exomes 𝑓: 0.24 ( 23421 hom. 81019 hem. )

Consequence

DGKK
NM_001013742.4 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKK	NM_001013742.4	MANE Select	c.2118+8C>T		splice_region intron	N/A	NP_001013764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKK	ENST00000611977.2	TSL:1 MANE Select	c.2118+8C>T		splice_region intron	N/A	ENSP00000477515.1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

30476

AN:

111003

Hom.:

3325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.0899

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.290

GnomAD2 exomes

AF:

0.263

AC:

45445

AN:

172595

AF XY:

0.236

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.0896

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.243

AC:

260025

AN:

1071514

Hom.:

23421

Cov.:

AF XY:

0.237

AC XY:

81019

AN XY:

342188

show subpopulations

African (AFR)

AF:

0.352

AC:

9099

AN:

25817

American (AMR)

AF:

0.449

AC:

15494

AN:

34507

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

7672

AN:

19136

East Asian (EAS)

AF:

0.129

AC:

3873

AN:

30014

South Asian (SAS)

AF:

0.142

AC:

7519

AN:

52938

European-Finnish (FIN)

AF:

0.196

AC:

7874

AN:

40125

Middle Eastern (MID)

AF:

0.326

AC:

1324

AN:

4057

European-Non Finnish (NFE)

AF:

0.239

AC:

196128

AN:

819727

Other (OTH)

AF:

0.244

AC:

11042

AN:

45193

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

5872

11744

17617

23489

29361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6970

13940

20910

27880

34850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.275

AC:

30486

AN:

111059

Hom.:

3324

Cov.:

AF XY:

0.262

AC XY:

8727

AN XY:

33331

show subpopulations

African (AFR)

AF:

0.338

AC:

10296

AN:

30492

American (AMR)

AF:

0.334

AC:

3506

AN:

10483

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1045

AN:

2637

East Asian (EAS)

AF:

0.0896

AC:

316

AN:

3527

South Asian (SAS)

AF:

0.137

AC:

361

AN:

2628

European-Finnish (FIN)

AF:

0.180

AC:

1079

AN:

6008

Middle Eastern (MID)

AF:

0.384

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.248

AC:

13090

AN:

52878

Other (OTH)

AF:

0.289

AC:

436

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

781

1561

2342

3122

3903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.272

Hom.:

27871

Bravo

AF:

0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.4

(source)

DANN

Benign

0.57

PhyloP100

1.5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over