chr4-961800-G-T

Position:

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

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37
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]

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ACMG classification

Classification made for transcript

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 Protein UniProt
DGKQNM_001347.4 linkuse as main transcriptc.2350C>A p.Leu784Met missense_variant 20/23 ENST00000273814.8 NP_001338.2
DGKQXM_047449687.1 linkuse as main transcriptc.2437C>A p.Leu813Met missense_variant 20/23 XP_047305643.1
DGKQXM_011513411.2 linkuse as main transcriptc.2350C>A p.Leu784Met missense_variant 20/23 XP_011511713.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGKQENST00000273814.8 linkuse as main transcriptc.2350C>A p.Leu784Met missense_variant 20/231 NM_001347.4 ENSP00000273814 P1
DGKQENST00000509465.5 linkuse as main transcriptc.2152C>A p.Leu718Met missense_variant 19/225 ENSP00000425862
DGKQENST00000515182.1 linkuse as main transcriptc.107+182C>A intron_variant 5 ENSP00000421756

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 18, 2021The 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; API