13-42159244-C-CTTTTTTTTTTTTTTT

Position:

• chr13-42159244-C-CTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PVS1_Moderate BP6_Moderate BS2

The NM_178009.5(DGKH):​c.623-17_623-3dupTTTTTTTTTTTTTTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (38 hom., cov: 0)
  • Exomes 𝑓: 0.0057 (281 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGKH NM_178009.5 splice_acceptor, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0540

Genes affected

DGKH (HGNC:2854): (diacylglycerol kinase eta) This gene encodes a member of the diacylglycerol kinase (DGK) enzyme family. Members of this family are involved in regulating intracellular concentrations of diacylglycerol and phosphatidic acid. Variation in this gene has been associated with bipolar disorder. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2014]

DGKH (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.028938029 fraction of the gene. Cryptic splice site detected, with MaxEntScore 11, offset of 0 (no position change), new splice context is: ttttttttttttttttttAGtgt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BP6: Variant 13-42159244-C-CTTTTTTTTTTTTTTT is Benign according to our data. Variant chr13-42159244-C-CTTTTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 2643782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 179 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKH	NM_178009.5	c.623-17_623-3dupTTTTTTTTTTTTTTT		splice_acceptor_variant, intron_variant		ENST00000337343.9	NP_821077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.623-17_623-3dupTTTTTTTTTTTTTTT		splice_acceptor_variant, intron_variant		1	NM_178009.5	ENSP00000337572.4

Frequencies

GnomAD3 genomes AF: 0.00282 AC: 179 AN: 63392 Hom.: 38 Cov.: 0

Gnomad AFR AF: 0.00581

Gnomad AMI AF: 0.00211

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.00365

Gnomad EAS AF: 0.00596

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.00252

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00572 AC: 870 AN: 152048 Hom.: 281 Cov.: 15 AF XY: 0.00591 AC XY: 483 AN XY: 81688

Gnomad4 AFR exome AF: 0.00413

Gnomad4 AMR exome AF: 0.00977

Gnomad4 ASJ exome AF: 0.00681

Gnomad4 EAS exome AF: 0.00346

Gnomad4 SAS exome AF: 0.00723

Gnomad4 FIN exome AF: 0.00459

Gnomad4 NFE exome AF: 0.00536

Gnomad4 OTH exome AF: 0.00787

GnomAD4 genome AF: 0.00282 AC: 179 AN: 63388 Hom.: 38 Cov.: 0 AF XY: 0.00305 AC XY: 85 AN XY: 27840

Gnomad4 AFR AF: 0.00581

Gnomad4 AMR AF: 0.00132

Gnomad4 ASJ AF: 0.00365

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.00252

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

DGKH: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs57531279; hg19: chr13-42733380;