Genetic Variant DGKH:p.Glu1109Glu (chr13-42219343-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_178009.5(DGKH):c.3327G>A(p.Glu1109Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,612,736 control chromosomes in the GnomAD database, including 358,502 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 32614 hom., cov: 32)

Exomes 𝑓: 0.67 ( 325888 hom. )

Consequence

DGKH
NM_178009.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

19 publications found

Variant links:

Genes affected

DGKH (HGNC:2854): (diacylglycerol kinase eta) This gene encodes a member of the diacylglycerol kinase (DGK) enzyme family. Members of this family are involved in regulating intracellular concentrations of diacylglycerol and phosphatidic acid. Variation in this gene has been associated with bipolar disorder. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2014]

DGKH links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP7

Synonymous conserved (PhyloP=0.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKH	NM_178009.5 link	c.3327G>A	p.Glu1109Glu	synonymous_variant	Exon 27 of 30	ENST00000337343.9	NP_821077.1	Q86XP1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9 link	c.3327G>A	p.Glu1109Glu	synonymous_variant	Exon 27 of 30	1	NM_178009.5	ENSP00000337572.4		Q86XP1-1

Frequencies

GnomAD3 genomes

AF:

0.653

AC:

99240

AN:

151944

Hom.:

32598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.636

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.751

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.685

GnomAD2 exomes

AF:

0.642

AC:

160810

AN:

250580

AF XY:

0.638

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.573

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.766

Gnomad FIN exome

AF:

0.690

Gnomad NFE exome

AF:

0.675

Gnomad OTH exome

AF:

0.639

GnomAD4 exome

AF:

0.666

AC:

972170

AN:

1460674

Hom.:

325888

Cov.:

AF XY:

0.661

AC XY:

480024

AN XY:

726712

show subpopulations

African (AFR)

AF:

0.614

AC:

20548

AN:

33448

American (AMR)

AF:

0.576

AC:

25728

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.666

AC:

17387

AN:

26108

East Asian (EAS)

AF:

0.743

AC:

29460

AN:

39668

South Asian (SAS)

AF:

0.494

AC:

42536

AN:

86120

European-Finnish (FIN)

AF:

0.690

AC:

36810

AN:

53360

Middle Eastern (MID)

AF:

0.607

AC:

3493

AN:

5758

European-Non Finnish (NFE)

AF:

0.681

AC:

756888

AN:

1111204

Other (OTH)

AF:

0.652

AC:

39320

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

15467

30933

46400

61866

77333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19386

38772

58158

77544

96930

<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:

0.653

AC:

99295

AN:

152062

Hom.:

32614

Cov.:

AF XY:

0.652

AC XY:

48409

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.614

AC:

25450

AN:

41462

American (AMR)

AF:

0.635

AC:

9707

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

2305

AN:

3470

East Asian (EAS)

AF:

0.751

AC:

3885

AN:

5170

South Asian (SAS)

AF:

0.498

AC:

2397

AN:

4816

European-Finnish (FIN)

AF:

0.695

AC:

7340

AN:

10566

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.675

AC:

45909

AN:

67980

Other (OTH)

AF:

0.685

AC:

1447

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1792

3584

5377

7169

8961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.668

Hom.:

66929

Bravo

AF:

0.653

Asia WGS

AF:

0.627

AC:

2180

AN:

3478

EpiCase

AF:

0.675

EpiControl

AF:

0.670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

5.8

(source)

DANN

Benign

0.58

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over