7-14338608-T-C

Variant names:

• chr7-14338608-T-C
• rs935632689
• NM_001350709.2:c.2029A>G

Variant summary

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

The NM_001350709.2(DGKB):​c.2029A>G​(p.Lys677Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DGKB NM_001350709.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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

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 rank	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.2029A>G	p.Lys677Glu	missense_variant	Exon 23 of 26	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.2029A>G	p.Lys677Glu	missense_variant	Exon 23 of 26	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2032A>G (p.K678E) alteration is located in exon 22 (coding exon 22) of the DGKB gene. This alteration results from a A to G substitution at nucleotide position 2032, causing the lysine (K) at amino acid position 678 to be replaced by a glutamic acid (E). 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	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	1.0	D;.;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M;M;.;.;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	N;N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.12	T;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.99	D;D;.;.;P
Vest4		0.70
MutPred		0.52		Loss of methylation at K678 (P = 0.0068);Loss of methylation at K678 (P = 0.0068);.;.;Loss of methylation at K678 (P = 0.0068);
MVP		0.53
MPC		0.80
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.36
gMVP		0.68

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

Other links and lift over

dbSNP: rs935632689; hg19: chr7-14378233;