Variant 2-233354567-C-A 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.49C>A(p.Pro17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,061,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

DGKD
NM_152879.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.265

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:

Genome browser will be placed here

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=0.12375376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKD	NM_152879.3 linkuse as main transcript	c.49C>A	p.Pro17Thr	missense_variant	1/30	ENST00000264057.7	NP_690618.2	Q16760-1
DGKD	XM_047446097.1 linkuse as main transcript	c.49C>A	p.Pro17Thr	missense_variant	1/29		XP_047302053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DGKD	ENST00000264057.7 linkuse as main transcript	c.49C>A	p.Pro17Thr	missense_variant	1/30	1	NM_152879.3	ENSP00000264057.2	Q16760-1
DGKD	ENST00000427930.5 linkuse as main transcript	c.49C>A	p.Pro17Thr	missense_variant	1/4	5		ENSP00000407938.1	C9JY42
DGKD	ENST00000442524.4 linkuse as main transcript	c.-6C>A		upstream_gene_variant		3		ENSP00000485047.1	A0A096LNI6

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

145918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000640

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

42848

Hom.:

AF XY:

0.000154

AC XY:

AN XY:

26034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000359

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000349

AC:

320

AN:

915746

Hom.:

Cov.:

AF XY:

0.000372

AC XY:

163

AN XY:

438576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000130

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:

0.000390

Gnomad4 OTH exome

AF:

0.000164

GnomAD4 genome

AF:

0.000302

AC:

AN:

145918

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

70928

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000640

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.000276

ExAC

AF:

0.0000961

AC:

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

Jan 11, 2023

The c.49C>A (p.P17T) alteration is located in exon 1 (coding exon 1) of the DGKD gene. This alteration results from a C to A substitution at nucleotide position 49, causing the proline (P) at amino acid position 17 to be replaced by a threonine (T). 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

0.086

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.073

T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.022

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.12

T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

0.81

L;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.16

N;N

REVEL

Benign

0.14

Sift

Benign

0.074

T;D

Sift4G

Benign

0.53

T;T

Polyphen

0.043

B;.

Vest4

0.23

MVP

0.61

MPC

0.55

ClinPred

0.037

GERP RS

1.3

Varity_R

0.070

gMVP

0.46

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