7-14682763-C-T

Position:

• chr7-14682763-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001350709.2(DGKB):​c.908G>A​(p.Arg303Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DGKB NM_001350709.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.48

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07336128).
• BP6: Variant 7-14682763-C-T is Benign according to our data. Variant chr7-14682763-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3271710.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.908G>A	p.Arg303Lys	missense_variant	11/26	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.908G>A	p.Arg303Lys	missense_variant	11/26	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.55
DEOGEN2	Benign	0.034	T;T;.;.;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.69	T;.;T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.073	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.57	N;N;.;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.34	N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.86	T;T;T;T;T
Polyphen		0.0	B;B;.;.;B
Vest4		0.11
MutPred		0.43		Gain of methylation at R303 (P = 0.0189);Gain of methylation at R303 (P = 0.0189);Gain of methylation at R303 (P = 0.0189);.;Gain of methylation at R303 (P = 0.0189);
MVP		0.39
MPC		0.30
ClinPred		0.13	T
GERP RS		4.7
Varity_R		0.089
gMVP		0.13

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: rs1196598454; hg19: chr7-14722388; COSMIC: COSV104990908;