rs838709

Positions:

• chr2-233376098-C-A
• chr2-233376098-C-T

Variant summary

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

The NM_152879.3(DGKD):​c.157-12159C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 151,942 control chromosomes in the GnomAD database, including 42,448 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 0.74 (42448 hom., cov: 30)
• Consequence: DGKD NM_152879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

Genes affected

DGKD (HGNC:2851): (diacylglycerol kinase delta) This gene encodes a cytoplasmic enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. Diacylglycerol and phosphatidic acid are two lipids that act as second messengers in signaling cascades. Their cellular concentrations are regulated by the encoded protein, and so it is thought to play an important role in cellular signal transduction. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKD	NM_152879.3	c.157-12159C>A		intron_variant		ENST00000264057.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKD	ENST00000264057.7	c.157-12159C>A		intron_variant		1	NM_152879.3
DGKD	ENST00000427930.5	c.156+21424C>A		intron_variant		5
DGKD	ENST00000442524.4	c.104-12159C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112513 AN: 151824 Hom.: 42396 Cov.: 30

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.736

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.741 AC: 112616 AN: 151942 Hom.: 42448 Cov.: 30 AF XY: 0.739 AC XY: 54881 AN XY: 74222

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.739

Alfa AF: 0.702 Hom.: 73321

Bravo AF: 0.745

Asia WGS AF: 0.820 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.040
DANN	Benign	0.55

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: rs838709; hg19: chr2-234284744;