Genetic Variant NM_152879.3:c.25C>G (chr2-233354543-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152879.3(DGKD):c.25C>G(p.Pro9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000796 in 1,004,962 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000081 ( 1 hom. )

Consequence

DGKD
NM_152879.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.464

Publications

1 publications found

Variant links:

Genes affected

DGKD (HGNC:2851): (diacylglycerol kinase delta) This gene encodes a cytoplasmic enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. Diacylglycerol and phosphatidic acid are two lipids that act as second messengers in signaling cascades. Their cellular concentrations are regulated by the encoded protein, and so it is thought to play an important role in cellular signal transduction. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

DGKD links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06537339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152879.3. 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
	DGKD	NM_152879.3	MANE Select	c.25C>G	p.Pro9Ala	missense	Exon 1 of 30	NP_690618.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKD	ENST00000264057.7	TSL:1 MANE Select	c.25C>G	p.Pro9Ala	missense	Exon 1 of 30	ENSP00000264057.2	Q16760-1
DGKD	ENST00000963810.1		c.25C>G	p.Pro9Ala	missense	Exon 1 of 31	ENSP00000633869.1
DGKD	ENST00000963809.1		c.25C>G	p.Pro9Ala	missense	Exon 1 of 31	ENSP00000633868.1

Frequencies

GnomAD3 genomes

AF:

0.00000687

AC:

AN:

145636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

4412

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000815

AC:

AN:

859326

Hom.:

Cov.:

AF XY:

0.00000744

AC XY:

AN XY:

403144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16046

American (AMR)

AF:

0.00

AC:

AN:

1548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5646

East Asian (EAS)

AF:

0.00

AC:

AN:

4184

South Asian (SAS)

AF:

0.00

AC:

AN:

22300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1730

European-Non Finnish (NFE)

AF:

0.00000642

AC:

AN:

778576

Other (OTH)

AF:

0.0000709

AC:

AN:

28200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000687

AC:

AN:

145636

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40706

American (AMR)

AF:

0.00

AC:

AN:

14704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

4980

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

65544

Other (OTH)

AF:

0.00

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.074

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.085

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.84

MutationAssessor

Benign

-0.20

PhyloP100

-0.46

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.47

REVEL

Benign

0.23

Sift

Benign

1.0

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.18

MutPred

0.21

Loss of glycosylation at P9 (P = 0.0049)

MVP

0.49

MPC

0.48

ClinPred

0.032

GERP RS

-0.99

PromoterAI

0.077

Neutral

(source)

Varity_R

0.042

gMVP

0.35

Mutation Taster

=96/4

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over