Genetic Variant DGKD:p.Pro10Ser (chr2-233354546-C-T) – 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.28C>T(p.Pro10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 867,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. P10L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

DGKD
NM_152879.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

Publications

0 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=0.15798512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKD	NM_152879.3 link	c.28C>T	p.Pro10Ser	missense_variant	Exon 1 of 30	ENST00000264057.7	NP_690618.2	Q16760-1
DGKD	XM_047446097.1 link	c.28C>T	p.Pro10Ser	missense_variant	Exon 1 of 29		XP_047302053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DGKD	ENST00000264057.7 link	c.28C>T	p.Pro10Ser	missense_variant	Exon 1 of 30	1	NM_152879.3	ENSP00000264057.2	Q16760-1
DGKD	ENST00000427930.5 link	c.28C>T	p.Pro10Ser	missense_variant	Exon 1 of 4	5		ENSP00000407938.1	C9JY42
DGKD	ENST00000442524.4 link	c.-27C>T		upstream_gene_variant		3		ENSP00000485047.1	A0A096LNI6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000346

AC:

AN:

867294

Hom.:

Cov.:

AF XY:

0.00000489

AC XY:

AN XY:

408588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16184

American (AMR)

AF:

0.00

AC:

AN:

2090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5952

East Asian (EAS)

AF:

0.00

AC:

AN:

4264

South Asian (SAS)

AF:

0.00

AC:

AN:

24022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1744

European-Non Finnish (NFE)

AF:

0.00000383

AC:

AN:

783054

Other (OTH)

AF:

0.00

AC:

AN:

28516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.050

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.55

N;.

PhyloP100

1.4

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.19

Sift

Benign

0.13

T;D

Sift4G

Benign

0.15

T;T

Polyphen

0.0060

B;.

Vest4

0.15

MutPred

0.34

Gain of phosphorylation at P10 (P = 0.0012);Gain of phosphorylation at P10 (P = 0.0012);

MVP

0.50

MPC

0.50

ClinPred

0.033

GERP RS

-1.2

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.051

gMVP

0.42

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over