Genetic Variant DGKD:p.Pro33Arg (chr2-233354616-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152879.3(DGKD):c.98C>G(p.Pro33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P33S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DGKD
NM_152879.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23688203).

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.98C>G	p.Pro33Arg	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.98C>G	p.Pro33Arg	missense	Exon 1 of 30	ENSP00000264057.2	Q16760-1
DGKD	ENST00000963810.1		c.98C>G	p.Pro33Arg	missense	Exon 1 of 31	ENSP00000633869.1
DGKD	ENST00000963809.1		c.98C>G	p.Pro33Arg	missense	Exon 1 of 31	ENSP00000633868.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

982914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

478084

African (AFR)

AF:

0.00

AC:

AN:

19228

American (AMR)

AF:

0.00

AC:

AN:

16290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12102

East Asian (EAS)

AF:

0.00

AC:

AN:

6490

South Asian (SAS)

AF:

0.00

AC:

AN:

47378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2626

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

838986

Other (OTH)

AF:

0.00

AC:

AN:

33354

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.15

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.23

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.24

MetaSVM

Uncertain

0.30

MutationAssessor

Benign

0.81

PhyloP100

-0.030

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.31

Sift

Benign

0.044

Sift4G

Uncertain

0.028

Polyphen

0.99

Vest4

0.076

MutPred

0.21

Gain of helix (P = 0.005)

MVP

0.74

MPC

0.52

ClinPred

0.53

GERP RS

1.3

PromoterAI

0.0046

Neutral

(source)

Varity_R

0.087

gMVP

0.44

Mutation Taster

=78/22

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over