13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Position:

• chr13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

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.623-3_623-2insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT 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 0.0010 (20 hom., cov: 0)
  • Exomes 𝑓: 0.00051 (27 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-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT is Benign according to our data. Variant chr13-42159244-C-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 2643789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 64 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 64 AN: 63402 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.000838

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.000521

Gnomad EAS AF: 0.00298

Gnomad SAS AF: 0.000580

Gnomad FIN AF: 0.00269

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000513 AC: 78 AN: 152094 Hom.: 27 Cov.: 15 AF XY: 0.000465 AC XY: 38 AN XY: 81704

Gnomad4 AFR exome AF: 0.000138

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.000233

Gnomad4 FIN exome AF: 0.000706

Gnomad4 NFE exome AF: 0.000704

Gnomad4 OTH exome AF: 0.000387

GnomAD4 genome AF: 0.00101 AC: 64 AN: 63398 Hom.: 20 Cov.: 0 AF XY: 0.00101 AC XY: 28 AN XY: 27842

Gnomad4 AFR AF: 0.000837

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.000521

Gnomad4 EAS AF: 0.00299

Gnomad4 SAS AF: 0.000583

Gnomad4 FIN AF: 0.00269

Gnomad4 NFE AF: 0.00115

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

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;