rs2279465

Variant names:

• chr11-46377988-T-C
• rs2279465
• ENST00000527211.5:n.1469T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000527211.5(DGKZ):​n.1469T>C variant causes a non coding transcript exon 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 ENST00000527211.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DGKZ	NM_001199267.2	c.2340-210T>C		intron_variant	Intron 25 of 30	ENST00000456247.7	NP_001186196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKZ	ENST00000456247.7	c.2340-210T>C		intron_variant	Intron 25 of 30	1	NM_001199267.2	ENSP00000395684.2

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

African (AFR) AF: 0.394 AC: 5132 AN: 13022

American (AMR) AF: 0.103 AC: 2246 AN: 21818

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 2553 AN: 14388

East Asian (EAS) AF: 0.0623 AC: 1922 AN: 30864

South Asian (SAS) AF: 0.158 AC: 7553 AN: 47882

European-Finnish (FIN) AF: 0.126 AC: 3714 AN: 29558

Middle Eastern (MID) AF: 0.214 AC: 516 AN: 2416

European-Non Finnish (NFE) AF: 0.168 AC: 48185 AN: 286000

Other (OTH) AF: 0.180 AC: 4841 AN: 26842

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

African (AFR) AF: 0.398 AC: 16490 AN: 41482

American (AMR) AF: 0.140 AC: 2138 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3472

East Asian (EAS) AF: 0.0651 AC: 338 AN: 5190

South Asian (SAS) AF: 0.151 AC: 730 AN: 4830

European-Finnish (FIN) AF: 0.120 AC: 1279 AN: 10616

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11719 AN: 68016

Other (OTH) AF: 0.206 AC: 436 AN: 2116

Alfa AF: 0.142 Hom.: 386

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
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2279465; hg19: chr11-46399538;