Genetic Variant DGKG:p.Val697Leu (chr3-186188208-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_001346.3(DGKG):c.2089G>C(p.Val697Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V697I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DGKG
NM_001346.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

0 publications found

Variant links:

Genes affected

DGKG (HGNC:2853): (diacylglycerol kinase gamma) This gene encodes an enzyme that is a member of the type I subfamily of diacylglycerol kinases, which are involved in lipid metabolism. These enzymes generate phosphatidic acid by catalyzing the phosphorylation of diacylglycerol, a fundamental lipid second messenger that activates numerous proteins, including protein kinase C isoforms, Ras guanyl nucleotide-releasing proteins and some transient receptor potential channels. Diacylglycerol kinase gamma has been implicated in cell cycle regulation and in the negative regulation of macrophage differentiation in leukemia cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DGKG 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=0.14846611).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKG	NM_001346.3	MANE Select	c.2089G>C	p.Val697Leu	missense	Exon 22 of 25	NP_001337.2	P49619-1
DGKG	NM_001080744.2		c.2014G>C	p.Val672Leu	missense	Exon 21 of 24	NP_001074213.1	P49619-2
DGKG	NM_001080745.2		c.1972G>C	p.Val658Leu	missense	Exon 21 of 24	NP_001074214.1	P49619-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKG	ENST00000265022.8	TSL:1 MANE Select	c.2089G>C	p.Val697Leu	missense	Exon 22 of 25	ENSP00000265022.3	P49619-1
DGKG	ENST00000344484.8	TSL:1	c.2014G>C	p.Val672Leu	missense	Exon 21 of 24	ENSP00000339777.4	P49619-2
DGKG	ENST00000480809.5	TSL:1	n.2446G>C		non_coding_transcript_exon	Exon 22 of 24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.12

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.81

M_CAP

Benign

0.0090

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.030

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

REVEL

Benign

0.034

Sift

Benign

0.11

Sift4G

Benign

0.61

Polyphen

0.011

Vest4

0.24

MutPred

0.50

Gain of catalytic residue at V697 (P = 0.0043)

MVP

0.27

MPC

0.099

ClinPred

0.11

GERP RS

-3.0

Varity_R

0.11

gMVP

0.43

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

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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