rs2291615

Positions:

• chr12-55941366-G-A

Variant summary

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

The NM_001345.5(DGKA):​c.1175+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,602,570 control chromosomes in the GnomAD database, including 66,656 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 0.21 (4376 hom., cov: 31)
  • Exomes 𝑓: 0.29 (62280 hom.)
• Consequence: DGKA NM_001345.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

DGKA (HGNC:2849): (diacylglycerol kinase alpha) The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and phosphorylating diacylglycerol to phosphatidic acid. Several transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKA	NM_001345.5	c.1175+41G>A		intron_variant		ENST00000331886.10	NP_001336.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKA	ENST00000331886.10	c.1175+41G>A		intron_variant		5	NM_001345.5	ENSP00000328405	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32495 AN: 151946 Hom.: 4379 Cov.: 31

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.265 AC: 65938 AN: 248914 Hom.: 9667 AF XY: 0.280 AC XY: 37690 AN XY: 134546

Gnomad AFR exome AF: 0.0490

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.295

Gnomad SAS exome AF: 0.396

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.287 AC: 416622 AN: 1450506 Hom.: 62280 Cov.: 30 AF XY: 0.292 AC XY: 210693 AN XY: 720776

Gnomad4 AFR exome AF: 0.0440

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.214 AC: 32474 AN: 152064 Hom.: 4376 Cov.: 31 AF XY: 0.213 AC XY: 15795 AN XY: 74306

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.216

Alfa AF: 0.254 Hom.: 2216

Bravo AF: 0.201

Asia WGS AF: 0.355 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.84

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: rs2291615; hg19: chr12-56335150;