chr7-14621393-A-T

Position:

• chr7-14621393-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001350709.2(DGKB):​c.1269T>A​(p.Asp423Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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: 0.788

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14934716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.1269T>A	p.Asp423Glu	missense_variant	15/26	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.1269T>A	p.Asp423Glu	missense_variant	15/26	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.1272T>A (p.D424E) alteration is located in exon 14 (coding exon 14) of the DGKB gene. This alteration results from a T to A substitution at nucleotide position 1272, causing the aspartic acid (D) at amino acid position 424 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	Benign	0.32
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.084	T;T;.;.;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T;.;T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M;M;.;.;M
MutationTaster	Benign	0.82	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.31	T;T;T;T;T
Sift4G	Benign	0.51	T;T;T;T;T
Polyphen		0.0070	B;B;.;.;B
Vest4		0.36
MutPred		0.29		Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);.;.;Gain of helix (P = 0.0164);
MVP		0.70
MPC		0.30
ClinPred		0.59	D
GERP RS		2.4
Varity_R		0.095
gMVP		0.23

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: chr7-14661018;