13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Position:

• chr13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

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_623-2insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 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 0.00073 (15 hom., cov: 0)
  • Exomes 𝑓: 0.00085 (48 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-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT is Benign according to our data. Variant chr13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 2643787.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_623-2insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		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_623-2insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		splice_acceptor_variant, intron_variant		1	NM_178009.5	ENSP00000337572.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 46 AN: 63404 Hom.: 15 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000524

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000528

Gnomad ASJ AF: 0.00104

Gnomad EAS AF: 0.000497

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000875

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000855 AC: 130 AN: 152092 Hom.: 48 Cov.: 15 AF XY: 0.000857 AC XY: 70 AN XY: 81702

Gnomad4 AFR exome AF: 0.000138

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000568

Gnomad4 EAS exome AF: 0.00157

Gnomad4 SAS exome AF: 0.000420

Gnomad4 FIN exome AF: 0.000353

Gnomad4 NFE exome AF: 0.00101

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000726 AC: 46 AN: 63400 Hom.: 15 Cov.: 0 AF XY: 0.000826 AC XY: 23 AN XY: 27844

Gnomad4 AFR AF: 0.000523

Gnomad4 AMR AF: 0.000528

Gnomad4 ASJ AF: 0.00104

Gnomad4 EAS AF: 0.000498

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.000875

Gnomad4 OTH AF: 0.00

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

Nov 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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-42733380;