Genetic Variant DGKH:c.855+117C>G (chr13-42160253-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_178009.5(DGKH):c.855+117C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,354,792 control chromosomes in the GnomAD database, including 16,432 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 0.12 ( 1419 hom., cov: 32)

Exomes 𝑓: 0.15 ( 15013 hom. )

Consequence

DGKH
NM_178009.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.231

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178009.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DGKH	NM_178009.5	MANE Select	c.855+117C>G	intron	N/A	NP_821077.1
DGKH	NM_001204504.3		c.855+117C>G	intron	N/A	NP_001191433.1
DGKH	NM_152910.6		c.855+117C>G	intron	N/A	NP_690874.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DGKH	ENST00000337343.9	TSL:1 MANE Select	c.855+117C>G	intron	N/A	ENSP00000337572.4
DGKH	ENST00000261491.9	TSL:1	c.855+117C>G	intron	N/A	ENSP00000261491.4
DGKH	ENST00000536612.3	TSL:1	c.447+117C>G	intron	N/A	ENSP00000445114.2

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18244

AN:

152116

Hom.:

1418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.0866

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.153

AC:

184315

AN:

1202558

Hom.:

15013

AF XY:

0.154

AC XY:

93401

AN XY:

604570

show subpopulations

African (AFR)

AF:

0.0334

AC:

951

AN:

28456

American (AMR)

AF:

0.129

AC:

5433

AN:

42252

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

3903

AN:

22454

East Asian (EAS)

AF:

0.0993

AC:

3799

AN:

38254

South Asian (SAS)

AF:

0.174

AC:

13009

AN:

74760

European-Finnish (FIN)

AF:

0.110

AC:

4843

AN:

43934

Middle Eastern (MID)

AF:

0.164

AC:

857

AN:

5210

European-Non Finnish (NFE)

AF:

0.161

AC:

143808

AN:

895646

Other (OTH)

AF:

0.149

AC:

7712

AN:

51592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7608

15217

22825

30434

38042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4670

9340

14010

18680

23350

<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:

0.120

AC:

18255

AN:

152234

Hom.:

1419

Cov.:

AF XY:

0.119

AC XY:

8868

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0385

AC:

1600

AN:

41562

American (AMR)

AF:

0.144

AC:

2198

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

582

AN:

3470

East Asian (EAS)

AF:

0.0866

AC:

449

AN:

5182

South Asian (SAS)

AF:

0.181

AC:

872

AN:

4816

European-Finnish (FIN)

AF:

0.102

AC:

1083

AN:

10602

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10945

AN:

67998

Other (OTH)

AF:

0.169

AC:

357

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

821

1641

2462

3282

4103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.0377

Hom.:

Bravo

AF:

0.120

Asia WGS

AF:

0.129

AC:

449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.87

(source)

DANN

Benign

0.30

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over