rs2059320

Positions:

• chr7-137740025-C-T

Variant summary

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

The NM_001321708.2(DGKI):​c.402-50023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,072 control chromosomes in the GnomAD database, including 6,954 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 0.23 (6954 hom., cov: 32)
• Consequence: DGKI NM_001321708.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

Genes affected

DGKI (HGNC:2855): (diacylglycerol kinase iota) This gene is a member of the type IV diacylglycerol kinase subfamily. Diacylglycerol kinases regulate the intracellular concentration of diacylglycerol through its phosphorylation, producing phosphatidic acid. The specific role of the enzyme encoded by this gene is undetermined, however, it may play a crucial role in the production of phosphatidic acid in the retina or in recessive forms of retinal degeneration. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKI	NM_001321708.2	c.402-50023G>A		intron_variant		ENST00000614521.2	NP_001308637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKI	ENST00000614521.2	c.402-50023G>A		intron_variant		5	NM_001321708.2	ENSP00000479053	P3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34127 AN: 151954 Hom.: 6921 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.225 AC: 34225 AN: 152072 Hom.: 6954 Cov.: 32 AF XY: 0.226 AC XY: 16838 AN XY: 74352

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.189

Alfa AF: 0.111 Hom.: 1157

Bravo AF: 0.249

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.51

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: rs2059320; hg19: chr7-137424771;