Variant X-50382602-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001013742.4(DGKK):c.2551C>T(p.Arg851Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,190,741 control chromosomes in the GnomAD database, including 95 homozygotes. There are 1,065 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 48 hom., 542 hem., cov: 24)

Exomes 𝑓: 0.0019 ( 47 hom. 523 hem. )

Consequence

DGKK
NM_001013742.4 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.18

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016780794).

BP6

Variant X-50382602-G-A is Benign according to our data. Variant chrX-50382602-G-A is described in ClinVar as [Benign]. Clinvar id is 785699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKK	NM_001013742.4 linkuse as main transcript	c.2551C>T	p.Arg851Cys	missense_variant, splice_region_variant	18/28	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.2551C>T	p.Arg851Cys	missense_variant, splice_region_variant	18/28	1	NM_001013742.4	ENSP00000477515.1		Q5KSL6

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

1998

AN:

111789

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

545

AN XY:

33985

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00598

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000376

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00996

GnomAD3 exomes

AF:

0.00485

AC:

837

AN:

172620

Hom.:

AF XY:

0.00351

AC XY:

209

AN XY:

59486

show subpopulations

Gnomad AFR exome

AF:

0.0603

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000606

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000153

Gnomad OTH exome

AF:

0.00190

GnomAD4 exome

AF:

0.00187

AC:

2018

AN:

1078899

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

523

AN XY:

345551

show subpopulations

Gnomad4 AFR exome

AF:

0.0632

Gnomad4 AMR exome

AF:

0.00319

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000483

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.0178

AC:

1995

AN:

111842

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

542

AN XY:

34048

show subpopulations

Gnomad4 AFR

AF:

0.0621

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000377

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00984

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.0210

ESP6500AA

AF:

0.0571

AC:

180

ESP6500EA

AF:

0.000156

AC:

ExAC

AF:

0.00518

AC:

626

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0017

PrimateAI

Benign

0.29

Sift4G

Benign

0.13

Polyphen

0.036

Vest4

0.048

MVP

0.18

GERP RS

1.1

Varity_R

0.15

gMVP

0.58

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