Variant 4-961189-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001347.4(DGKQ):c.2587G>A(p.Gly863Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000424 in 1,416,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

DGKQ
NM_001347.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

DGKQ (HGNC:2856): (diacylglycerol kinase theta) The protein encoded by this gene contains three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain. It is localized in the speckle domains of the nucleus, and mediates the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. [provided by RefSeq, Jul 2008]

DGKQ links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034958363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DGKQ	NM_001347.4 linkuse as main transcript	c.2587G>A	p.Gly863Ser	missense_variant	22/23	ENST00000273814.8	NP_001338.2
DGKQ	XM_047449687.1 linkuse as main transcript	c.2674G>A	p.Gly892Ser	missense_variant	22/23		XP_047305643.1
DGKQ	XM_011513411.2 linkuse as main transcript	c.2587G>A	p.Gly863Ser	missense_variant	22/23		XP_011511713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DGKQ	ENST00000273814.8 linkuse as main transcript	c.2587G>A	p.Gly863Ser	missense_variant	22/23	1	NM_001347.4	ENSP00000273814	P1
DGKQ	ENST00000509465.5 linkuse as main transcript	c.2389G>A	p.Gly797Ser	missense_variant	21/22	5		ENSP00000425862
DGKQ	ENST00000515182.1 linkuse as main transcript	c.232G>A	p.Gly78Ser	missense_variant	4/5	5		ENSP00000421756

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

198432

Hom.:

AF XY:

0.0000186

AC XY:

AN XY:

107718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000248

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000424

AC:

AN:

1416578

Hom.:

Cov.:

AF XY:

0.00000428

AC XY:

AN XY:

700942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000130

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.17e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

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

Oct 14, 2023

The c.2587G>A (p.G863S) alteration is located in exon 22 (coding exon 22) of the DGKQ gene. This alteration results from a G to A substitution at nucleotide position 2587, causing the glycine (G) at amino acid position 863 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

0.076

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.90

D;D

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

N;.

MutationTaster

Benign

0.77

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.89

N;N

REVEL

Benign

0.067

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.12

B;.

Vest4

0.20

MutPred

0.56

Gain of MoRF binding (P = 0.0904);.;

MVP

0.23

MPC

0.29

ClinPred

0.13

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.34

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