12-55936553-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001345.5(DGKA):ā€‹c.50A>Gā€‹(p.Gln17Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000038 ( 0 hom. )

Consequence

DGKA
NM_001345.5 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22
Variant links:
Genes affected
DGKA (HGNC:2849): (diacylglycerol kinase alpha) The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and phosphorylating diacylglycerol to phosphatidic acid. Several transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.27612358).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DGKANM_001345.5 linkuse as main transcriptc.50A>G p.Gln17Arg missense_variant 2/24 ENST00000331886.10 NP_001336.2 P23743-1A0A024RB23

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DGKAENST00000331886.10 linkuse as main transcriptc.50A>G p.Gln17Arg missense_variant 2/245 NM_001345.5 ENSP00000328405.5 P23743-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000597
AC:
15
AN:
251438
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000376
AC:
55
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.0000399
AC XY:
29
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00122
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152176
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000247
AC:
3

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 GeneticsJun 17, 2024The c.50A>G (p.Q17R) alteration is located in exon 2 (coding exon 1) of the DGKA gene. This alteration results from a A to G substitution at nucleotide position 50, causing the glutamine (Q) at amino acid position 17 to be replaced by an arginine (R). 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
Uncertain
0.37
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;T;T;.;T;.;T;.;T;T;.;.;T;T;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;T;.;.;T;T;D;.;D;.;D;D;.;.;D
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.28
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Pathogenic
2.9
.;.;M;.;.;.;.;.;M;M;.;.;.;.;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.8
D;D;N;D;D;N;N;D;N;N;D;D;D;D;D
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D;.;D;D;.;T;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;.;D;D;D;T;D;D;D;D;D;D;D;D;D
Polyphen
0.96, 0.069
.;.;P;.;.;B;.;.;P;P;.;.;.;.;.
Vest4
0.52, 0.40
MutPred
0.39
Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);Gain of catalytic residue at Q15 (P = 0.0102);
MVP
0.86
MPC
1.5
ClinPred
0.88
D
GERP RS
4.9
Varity_R
0.46
gMVP
0.79

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: rs774720561; hg19: chr12-56330337; API