Genetic Variant DGKD:p.Pro17Ala (chr2-233354567-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.49C>G(p.Pro17Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17T) 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.265

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:

Genome browser will be placed here

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=0.115656614).

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.49C>G	p.Pro17Ala	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.49C>G	p.Pro17Ala	missense	Exon 1 of 30	ENSP00000264057.2	Q16760-1
DGKD	ENST00000963810.1		c.49C>G	p.Pro17Ala	missense	Exon 1 of 31	ENSP00000633869.1
DGKD	ENST00000963809.1		c.49C>G	p.Pro17Ala	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:

915746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

438576

African (AFR)

AF:

0.00

AC:

AN:

17130

American (AMR)

AF:

0.00

AC:

AN:

7682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9564

East Asian (EAS)

AF:

0.00

AC:

AN:

4576

South Asian (SAS)

AF:

0.00

AC:

AN:

35500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3814

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2014

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

804958

Other (OTH)

AF:

0.00

AC:

AN:

30508

GnomAD4 genome

Cov.:

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

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.073

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.021

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.34

PhyloP100

0.27

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.22

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.019

Vest4

0.14

MutPred

0.31

Loss of glycosylation at P17 (P = 7e-04)

MVP

0.61

MPC

0.48

ClinPred

0.047

GERP RS

1.3

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.043

gMVP

0.36

Mutation Taster

=95/5

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