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7-14736117-G-C

Variant summary

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

The NM_001350709.2(DGKB):c.246C>G(p.His82Gln) 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

DGKB
NM_001350709.2 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.803
Variant links:
Genes affected
DGKB (HGNC:2850): (diacylglycerol kinase beta) Diacylglycerol kinases (DGKs) are regulators of the intracellular concentration of the second messenger diacylglycerol (DAG) and thus play a key role in cellular processes. Nine mammalian isotypes have been identified, which are encoded by separate genes. Mammalian DGK isozymes contain a conserved catalytic (kinase) domain and a cysteine-rich domain (CRD). The protein encoded by this gene is a diacylglycerol kinase, beta isotype. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

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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 UniProt
DGKBNM_001350709.2 linkuse as main transcriptc.246C>G p.His82Gln missense_variant 5/26 ENST00000402815.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DGKBENST00000402815.6 linkuse as main transcriptc.246C>G p.His82Gln missense_variant 5/265 NM_001350709.2 P4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
28
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 GeneticsFeb 07, 2023The c.246C>G (p.H82Q) alteration is located in exon 4 (coding exon 4) of the DGKB gene. This alteration results from a C to G substitution at nucleotide position 246, causing the histidine (H) at amino acid position 82 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
Uncertain
0.53
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
Cadd
Benign
19
Dann
Uncertain
0.99
DEOGEN2
Benign
0.31
T;T;.;.;.
Eigen
Benign
-0.019
Eigen_PC
Benign
0.0073
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.80
T;.;T;T;T
M_CAP
Benign
0.045
D
MetaRNN
Uncertain
0.57
D;D;D;D;D
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
1.9
L;L;.;.;L
MutationTaster
Benign
0.71
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-4.2
D;D;D;D;D
REVEL
Benign
0.17
Sift
Benign
0.090
T;T;T;T;T
Sift4G
Benign
0.14
T;T;T;T;T
Polyphen
0.97
D;D;.;.;B
Vest4
0.76
MutPred
0.42
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);
MVP
0.73
MPC
0.94
ClinPred
0.97
D
GERP RS
0.92
Varity_R
0.39
gMVP
0.52

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: chr7-14775742; API