rs2279465

Positions:

• chr11-46377988-T-C

Variant summary

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

The NM_001199267.2(DGKZ):​c.2340-210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 625,016 control chromosomes in the GnomAD database, including 11,855 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 0.22 (4776 hom., cov: 33)
  • Exomes 𝑓: 0.16 (7079 hom.)
• Consequence: DGKZ NM_001199267.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

Genes affected

DGKZ (HGNC:2857): (diacylglycerol kinase zeta) The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It may attenuate protein kinase C activity by regulating diacylglycerol levels in intracellular signaling cascade and signal transduction. Alternative splicing occurs at this locus and multiple transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKZ	NM_001199267.2	c.2340-210T>C		intron_variant		ENST00000456247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKZ	ENST00000456247.7	c.2340-210T>C		intron_variant		1	NM_001199267.2	A1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34013 AN: 152108 Hom.: 4755 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0654

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.162 AC: 76662 AN: 472790 Hom.: 7079 Cov.: 5 AF XY: 0.161 AC XY: 40183 AN XY: 249242

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0623

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.224 AC: 34066 AN: 152226 Hom.: 4776 Cov.: 33 AF XY: 0.218 AC XY: 16250 AN XY: 74438

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.0651

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.206

Alfa AF: 0.133 Hom.: 326

Bravo AF: 0.232

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2279465; hg19: chr11-46399538;