rs762778462

Variant names:

• chr3-186188268-G-A
• rs762778462
• NM_001346.3:c.2029C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-186188268-G-A
• chr3-186188268-G-C
• chr3-186188268-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001346.3(DGKG):​c.2029C>T​(p.Arg677Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R677G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: DGKG NM_001346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 2 publications found

Genes affected

DGKG (HGNC:2853): (diacylglycerol kinase gamma) This gene encodes an enzyme that is a member of the type I subfamily of diacylglycerol kinases, which are involved in lipid metabolism. These enzymes generate phosphatidic acid by catalyzing the phosphorylation of diacylglycerol, a fundamental lipid second messenger that activates numerous proteins, including protein kinase C isoforms, Ras guanyl nucleotide-releasing proteins and some transient receptor potential channels. Diacylglycerol kinase gamma has been implicated in cell cycle regulation and in the negative regulation of macrophage differentiation in leukemia cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24143153).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKG	NM_001346.3	MANE Select	c.2029C>T	p.Arg677Trp	missense	Exon 22 of 25	NP_001337.2	P49619-1
	DGKG	NM_001080744.2		c.1954C>T	p.Arg652Trp	missense	Exon 21 of 24	NP_001074213.1	P49619-2
	DGKG	NM_001080745.2		c.1912C>T	p.Arg638Trp	missense	Exon 21 of 24	NP_001074214.1	P49619-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKG	ENST00000265022.8	TSL:1 MANE Select	c.2029C>T	p.Arg677Trp	missense	Exon 22 of 25	ENSP00000265022.3	P49619-1
	DGKG	ENST00000344484.8	TSL:1	c.1954C>T	p.Arg652Trp	missense	Exon 21 of 24	ENSP00000339777.4	P49619-2
	DGKG	ENST00000480809.5	TSL:1	n.2386C>T		non_coding_transcript_exon	Exon 22 of 24

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251488 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.0087
Eigen_PC	Benign	-0.0035
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.22
MutPred		0.64		Loss of disorder (P = 0.007)
MVP		0.66
MPC		0.44
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.72
gMVP		0.72
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs762778462; hg19: chr3-185906057;