13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Position:

• chr13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PVS1_Moderate BP6_Moderate

The NM_178009.5(DGKH):​c.623-3_623-2insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 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 0.0016 (33 hom., cov: 0)
  • Exomes 𝑓: 0.00086 (46 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 Uncertain_significance. Variant got 0 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-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT is Benign according to our data. Variant chr13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 2643786.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKH	NM_178009.5	c.623-3_623-2insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		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.623-3_623-2insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		splice_acceptor_variant, intron_variant		1	NM_178009.5	ENSP00000337572.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 100 AN: 63404 Hom.: 33 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00185

Gnomad ASJ AF: 0.00208

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.00252

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000861 AC: 131 AN: 152088 Hom.: 46 Cov.: 15 AF XY: 0.000918 AC XY: 75 AN XY: 81702

Gnomad4 AFR exome AF: 0.000688

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000568

Gnomad4 EAS exome AF: 0.000943

Gnomad4 SAS exome AF: 0.000280

Gnomad4 FIN exome AF: 0.000706

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.000258

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00158 AC: 100 AN: 63400 Hom.: 33 Cov.: 0 AF XY: 0.00154 AC XY: 43 AN XY: 27844

Gnomad4 AFR AF: 0.000628

Gnomad4 AMR AF: 0.00185

Gnomad4 ASJ AF: 0.00208

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00226

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

Dec 01, 2022

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;