rs2239626

Positions:

• chr3-186281095-T-C
• chr3-186281095-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346.3(DGKG):​c.595-351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 187,998 control chromosomes in the GnomAD database, including 18,484 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (16355 hom., cov: 32)
  • Exomes 𝑓: 0.32 (2129 hom.)
• Consequence: DGKG NM_001346.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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]

DGKG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKG	NM_001346.3	c.595-351A>G		intron_variant		ENST00000265022.8	NP_001337.2
DGKG	NM_001080744.2	c.595-351A>G		intron_variant			NP_001074213.1
DGKG	NM_001080745.2	c.595-351A>G		intron_variant			NP_001074214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKG	ENST00000265022.8	c.595-351A>G		intron_variant		1	NM_001346.3	ENSP00000265022.3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63439 AN: 151938 Hom.: 16314 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.317 AC: 11397 AN: 35942 Hom.: 2129 Cov.: 0 AF XY: 0.315 AC XY: 5957 AN XY: 18904

Gnomad4 AFR exome AF: 0.760

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.418 AC: 63534 AN: 152056 Hom.: 16355 Cov.: 32 AF XY: 0.409 AC XY: 30400 AN XY: 74360

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.402

Alfa AF: 0.316 Hom.: 13228

Bravo AF: 0.442

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.2
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2239626; hg19: chr3-185998884;