chr17-56834477-G-T

Position:

• chr17-56834477-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000284061.8(DGKE):​c.-19+217G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,306 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.056 (292 hom., cov: 34)
• Consequence: DGKE ENST00000284061.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.28

Genes affected

DGKE (HGNC:2852): (diacylglycerol kinase epsilon) Diacylglycerol kinases are thought to be involved mainly in the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. When expressed in mammalian cells, DGK-epsilon shows specificity for arachidonyl-containing diacylglycerol. DGK-epsilon is expressed predominantly in testis. [provided by RefSeq, Jul 2008]

C17orf67 (HGNC:27900): (chromosome 17 open reading frame 67) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-56834477-G-T is Benign according to our data. Variant chr17-56834477-G-T is described in ClinVar as [Benign]. Clinvar id is 1238240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKE	NM_003647.3	c.-19+217G>T		intron_variant		ENST00000284061.8	NP_003638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKE	ENST00000284061.8	c.-19+217G>T		intron_variant		1	NM_003647.3	ENSP00000284061	P1
DGKE	ENST00000572810.1	c.-19+217G>T		intron_variant		1		ENSP00000459295
DGKE	ENST00000576869.5	n.130+217G>T		intron_variant, non_coding_transcript_variant		1
C17orf67	ENST00000487705.1	n.285+4012C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8515 AN: 152188 Hom.: 290 Cov.: 34

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.0176

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0540

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

GnomAD4 genome AF: 0.0559 AC: 8520 AN: 152306 Hom.: 292 Cov.: 34 AF XY: 0.0562 AC XY: 4185 AN XY: 74480

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0736

Gnomad4 OTH AF: 0.0534

Alfa AF: 0.0674 Hom.: 40

Bravo AF: 0.0572

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 25, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs116997614; hg19: chr17-54911838;