NM_001350709.2:c.2326C>G

Variant names:

• chr7-14149217-G-C
• rs1781812572
• NM_001350709.2:c.2326C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001350709.2(DGKB):​c.2326C>G​(p.Gln776Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,676 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q776K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DGKB NM_001350709.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350709.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	NM_001350709.2	MANE Select	c.2326C>G	p.Gln776Glu	missense	Exon 26 of 26	NP_001337638.1	B5MBY2
	DGKB	NM_001350705.1		c.2329C>G	p.Gln777Glu	missense	Exon 26 of 26	NP_001337634.1	Q9Y6T7-1
	DGKB	NM_001350706.2		c.2329C>G	p.Gln777Glu	missense	Exon 26 of 26	NP_001337635.1	Q9Y6T7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	ENST00000402815.6	TSL:5 MANE Select	c.2326C>G	p.Gln776Glu	missense	Exon 26 of 26	ENSP00000384909.1	B5MBY2
	DGKB	ENST00000399322.7	TSL:5	c.2329C>G	p.Gln777Glu	missense	Exon 25 of 25	ENSP00000382260.3	Q9Y6T7-1
	DGKB	ENST00000403951.6	TSL:5	c.2329C>G	p.Gln777Glu	missense	Exon 26 of 26	ENSP00000385780.2	Q9Y6T7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460676 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726638

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111340

Other (OTH) AF: 0.00 AC: 0 AN: 60322

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.71
MutPred		0.25		Gain of ubiquitination at K775 (P = 0.0373)
MVP		0.54
MPC		1.1
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.54
gMVP		0.75
Mutation Taster		=34/66	disease causing

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

Other links and lift over

dbSNP: rs1781812572; hg19: chr7-14188842;