4-961746-C-G

Variant names:

• chr4-961746-C-G
• NM_001347.4:c.2404G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001347.4(DGKQ):​c.2404G>C​(p.Glu802Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DGKQ NM_001347.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2838647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKQ	NM_001347.4	c.2404G>C	p.Glu802Gln	missense_variant	Exon 20 of 23	ENST00000273814.8	NP_001338.2
DGKQ	XM_047449687.1	c.2491G>C	p.Glu831Gln	missense_variant	Exon 20 of 23		XP_047305643.1
DGKQ	XM_011513411.2	c.2404G>C	p.Glu802Gln	missense_variant	Exon 20 of 23		XP_011511713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKQ	ENST00000273814.8	c.2404G>C	p.Glu802Gln	missense_variant	Exon 20 of 23	1	NM_001347.4	ENSP00000273814.3
DGKQ	ENST00000509465.5	c.2203G>C	p.Glu735Gln	missense_variant	Exon 19 of 22	5		ENSP00000425862.1
DGKQ	ENST00000515182.1	c.108-168G>C		intron_variant	Intron 2 of 4	5		ENSP00000421756.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2404G>C (p.E802Q) alteration is located in exon 20 (coding exon 20) of the DGKQ gene. This alteration results from a G to C substitution at nucleotide position 2404, causing the glutamic acid (E) at amino acid position 802 to be replaced by a glutamine (Q). 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	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.12	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.059	T
Polyphen		0.16	B
Vest4		0.33
MutPred		0.60		Gain of MoRF binding (P = 0.0449);
MVP		0.53
MPC		0.16
ClinPred		0.88	D
GERP RS		5.3
Varity_R		0.27
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-955534;