4-961800-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001347.4(DGKQ):c.2350C>A(p.Leu784Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.37

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKQ	NM_001347.4	c.2350C>A	p.Leu784Met	missense_variant	20/23	ENST00000273814.8
DGKQ	XM_047449687.1	c.2437C>A	p.Leu813Met	missense_variant	20/23
DGKQ	XM_011513411.2	c.2350C>A	p.Leu784Met	missense_variant	20/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKQ	ENST00000273814.8	c.2350C>A	p.Leu784Met	missense_variant	20/23	1	NM_001347.4	P1
DGKQ	ENST00000509465.5	c.2152C>A	p.Leu718Met	missense_variant	19/22	5
DGKQ	ENST00000515182.1	c.107+182C>A		intron_variant		5

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

The c.2350C>A (p.L784M) alteration is located in exon 20 (coding exon 20) of the DGKQ gene. This alteration results from a C to A substitution at nucleotide position 2350, causing the leucine (L) at amino acid position 784 to be replaced by a methionine (M). 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	0.20
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.25
Sift	Benign	0.035	D
Sift4G	Uncertain	0.047	D
Polyphen		0.93	P
Vest4		0.53
MutPred		0.50		Loss of catalytic residue at L784 (P = 0.0076);
MVP		0.45
MPC		0.57
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.26
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-955588;