Genetic Variant NM_003647.3:c.-18-210G>A (chr17-56834568-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003647.3(DGKE):c.-18-210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,874 control chromosomes in the GnomAD database, including 31,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.64 ( 31852 hom., cov: 33)

Consequence

DGKE
NM_003647.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0130

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-56834568-G-A is Benign according to our data. Variant chr17-56834568-G-A is described in ClinVar as Benign. ClinVar VariationId is 1249672.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003647.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKE	NM_003647.3	MANE Select	c.-18-210G>A		intron	N/A	NP_003638.1	A1L4Q0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DGKE	ENST00000284061.8	TSL:1 MANE Select	c.-18-210G>A	intron	N/A	ENSP00000284061.3	P52429-1
DGKE	ENST00000572810.1	TSL:1	c.-18-210G>A	intron	N/A	ENSP00000459295.1	P52429-2
DGKE	ENST00000576869.5	TSL:1	n.131-210G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97663

AN:

151756

Hom.:

31853

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.696

Gnomad ASJ

AF:

0.683

Gnomad EAS

AF:

0.894

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.748

Gnomad NFE

AF:

0.661

Gnomad OTH

AF:

0.665

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.643

AC:

97701

AN:

151874

Hom.:

31852

Cov.:

AF XY:

0.644

AC XY:

47828

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.575

AC:

23851

AN:

41458

American (AMR)

AF:

0.696

AC:

10643

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

2367

AN:

3468

East Asian (EAS)

AF:

0.894

AC:

4570

AN:

5112

South Asian (SAS)

AF:

0.587

AC:

2826

AN:

4818

European-Finnish (FIN)

AF:

0.604

AC:

6377

AN:

10558

Middle Eastern (MID)

AF:

0.743

AC:

217

AN:

292

European-Non Finnish (NFE)

AF:

0.661

AC:

44874

AN:

67856

Other (OTH)

AF:

0.659

AC:

1389

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1730

3460

5189

6919

8649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.636

Hom.:

4590

Bravo

AF:

0.651

Asia WGS

AF:

0.707

AC:

2458

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.6

(source)

DANN

Benign

0.96

PhyloP100

0.013

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over