7-14736187-T-C

Variant summary

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

The NM_001350709.2(DGKB):c.176A>G(p.Asp59Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000705 in 1,418,390 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DGKB NM_001350709.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.72

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/exons	MANE	UniProt
DGKB	NM_001350709.2	c.176A>G	p.Asp59Gly	missense_variant	5/26	ENST00000402815.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKB	ENST00000402815.6	c.176A>G	p.Asp59Gly	missense_variant	5/26	5	NM_001350709.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418390 Hom.: 0 Cov.: 25 AF XY: 0.00000142 AC XY: 1 AN XY: 704118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.00

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

Jan 19, 2024

The c.176A>G (p.D59G) alteration is located in exon 4 (coding exon 4) of the DGKB gene. This alteration results from a A to G substitution at nucleotide position 176, causing the aspartic acid (D) at amino acid position 59 to be replaced by a glycine (G). 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	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
Cadd	Pathogenic	27
Dann	Benign	0.96
DEOGEN2	Benign	0.29	T;T;.;.;.;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;.;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.55	D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;.;.;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.35	T;T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T
Polyphen		0.83	P;P;.;.;B;.
Vest4		0.96
MutPred		0.44		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.87
MPC		0.40
ClinPred		0.81	D
GERP RS		6.0
Varity_R		0.46
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr7-14775812;