Variant chr2-233354615-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152879.3(DGKD):c.97C>T(p.Pro33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000222 in 1,128,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

DGKD
NM_152879.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2503913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKD	NM_152879.3 link	c.97C>T	p.Pro33Ser	missense_variant	1/30	ENST00000264057.7	NP_690618.2	Q16760-1
DGKD	XM_047446097.1 link	c.97C>T	p.Pro33Ser	missense_variant	1/29		XP_047302053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DGKD	ENST00000264057.7 link	c.97C>T	p.Pro33Ser	missense_variant	1/30	1	NM_152879.3	ENSP00000264057.2	Q16760-1
DGKD	ENST00000442524.4 link	c.43C>T	p.Pro15Ser	missense_variant	1/4	3		ENSP00000485047.1	A0A096LNI6
DGKD	ENST00000427930.5 link	c.97C>T	p.Pro33Ser	missense_variant	1/4	5		ENSP00000407938.1	C9JY42

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146120

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:

0.0000304

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000234

AC:

AN:

982500

Hom.:

Cov.:

AF XY:

0.0000188

AC XY:

AN XY:

477814

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000250

Gnomad4 OTH exome

AF:

0.0000600

GnomAD4 genome

AF:

0.0000137

AC:

AN:

146120

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

71040

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000304

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.97C>T (p.P33S) alteration is located in exon 1 (coding exon 1) of the DGKD gene. This alteration results from a C to T substitution at nucleotide position 97, causing the proline (P) at amino acid position 33 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.28

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.25

T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

0.81

L;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.050

T;T

Polyphen

0.98

D;.

Vest4

0.14

MutPred

0.20

Gain of phosphorylation at P33 (P = 0.0031);Gain of phosphorylation at P33 (P = 0.0031);

MVP

0.77

MPC

0.50

ClinPred

0.63

GERP RS

1.3

Varity_R

0.086

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over