7-14757699-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001350709.2(DGKB):c.103G>C(p.Glu35Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000623 in 1,605,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
DGKB
NM_001350709.2 missense
NM_001350709.2 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 5.79
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 |
---|---|---|---|---|---|---|---|
DGKB | NM_001350709.2 | c.103G>C | p.Glu35Gln | missense_variant | 3/26 | ENST00000402815.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGKB | ENST00000402815.6 | c.103G>C | p.Glu35Gln | missense_variant | 3/26 | 5 | NM_001350709.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152010Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000344 AC: 5AN: 1453704Hom.: 0 Cov.: 27 AF XY: 0.00000276 AC XY: 2AN XY: 723544
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152010Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74226
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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 submitter | clinical testing | Ambry Genetics | May 26, 2022 | The c.103G>C (p.E35Q) alteration is located in exon 2 (coding exon 2) of the DGKB gene. This alteration results from a G to C substitution at nucleotide position 103, causing the glutamic acid (E) at amino acid position 35 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;T
Polyphen
D;D;.;.;D;.
Vest4
MutPred
Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);Loss of solvent accessibility (P = 0.0224);
MVP
MPC
0.94
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at