chr4-962443-G-A

Position:

Variant summary

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

The NM_001347.4(DGKQ):​c.2206C>T​(p.Pro736Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000444 in 1,575,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

DGKQ
NM_001347.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85
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]

Genome browser will be placed here

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.2206C>T p.Pro736Ser missense_variant 18/23 ENST00000273814.8 NP_001338.2
DGKQXM_047449687.1 linkuse as main transcriptc.2293C>T p.Pro765Ser missense_variant 18/23 XP_047305643.1
DGKQXM_011513411.2 linkuse as main transcriptc.2206C>T p.Pro736Ser missense_variant 18/23 XP_011511713.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGKQENST00000273814.8 linkuse as main transcriptc.2206C>T p.Pro736Ser missense_variant 18/231 NM_001347.4 ENSP00000273814 P1
DGKQENST00000509465.5 linkuse as main transcriptc.2008C>T p.Pro670Ser missense_variant 17/225 ENSP00000425862
DGKQENST00000515182.1 linkuse as main transcript upstream_gene_variant 5 ENSP00000421756

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152230
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000102
AC:
2
AN:
195446
Hom.:
0
AF XY:
0.00000939
AC XY:
1
AN XY:
106506
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000670
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
0.00000351
AC:
5
AN:
1423466
Hom.:
0
Cov.:
32
AF XY:
0.00000283
AC XY:
2
AN XY:
706186
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.0000737
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000242
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152230
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 GeneticsDec 15, 2023The c.2206C>T (p.P736S) alteration is located in exon 18 (coding exon 18) of the DGKQ gene. This alteration results from a C to T substitution at nucleotide position 2206, causing the proline (P) at amino acid position 736 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
0.14
BayesDel_addAF
Uncertain
0.049
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.040
T
Eigen
Benign
0.14
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.91
D
M_CAP
Pathogenic
0.30
D
MetaRNN
Uncertain
0.62
D
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.31
Sift
Benign
0.20
T
Sift4G
Benign
0.47
T
Polyphen
1.0
D
Vest4
0.54
MutPred
0.34
Loss of catalytic residue at P736 (P = 0.0011);
MVP
0.84
MPC
0.48
ClinPred
0.74
D
GERP RS
4.5
Varity_R
0.076
gMVP
0.40

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.

Other links and lift over

dbSNP: rs1380526612; hg19: chr4-956231; API