Genetic Variant NM_001350709.2:c.2326C>A (chr7-14149217-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001350709.2(DGKB):c.2326C>A(p.Gln776Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DGKB
NM_001350709.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72

Publications

0 publications found

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]

DGKB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35800385).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKB	NM_001350709.2	MANE Select	c.2326C>A	p.Gln776Lys	missense	Exon 26 of 26	NP_001337638.1	B5MBY2
DGKB	NM_001350705.1		c.2329C>A	p.Gln777Lys	missense	Exon 26 of 26	NP_001337634.1	Q9Y6T7-1
DGKB	NM_001350706.2		c.2329C>A	p.Gln777Lys	missense	Exon 26 of 26	NP_001337635.1	Q9Y6T7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKB	ENST00000402815.6	TSL:5 MANE Select	c.2326C>A	p.Gln776Lys	missense	Exon 26 of 26	ENSP00000384909.1	B5MBY2
DGKB	ENST00000399322.7	TSL:5	c.2329C>A	p.Gln777Lys	missense	Exon 25 of 25	ENSP00000382260.3	Q9Y6T7-1
DGKB	ENST00000403951.6	TSL:5	c.2329C>A	p.Gln777Lys	missense	Exon 26 of 26	ENSP00000385780.2	Q9Y6T7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460676

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726638

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111340

Other (OTH)

AF:

0.00

AC:

AN:

60322

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.42

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.020

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.7

PhyloP100

5.7

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.27

Sift

Benign

0.15

Sift4G

Benign

0.092

Polyphen

0.99

Vest4

0.44

MutPred

0.24

Gain of methylation at Q777 (P = 0.0125)

MVP

0.46

MPC

1.1

ClinPred

0.97

GERP RS

5.7

Varity_R

0.62

gMVP

0.75

Mutation Taster

=32/68

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over