13-42201919-A-G

Variant names:

• chr13-42201919-A-G
• rs1170101
• NM_178009.5:c.2493+2010A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178009.5(DGKH):​c.2493+2010A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,974 control chromosomes in the GnomAD database, including 11,893 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11893 hom., cov: 31)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.2493+2010A>G		intron_variant	Intron 20 of 29	ENST00000337343.9	NP_821077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.2493+2010A>G		intron_variant	Intron 20 of 29	1	NM_178009.5	ENSP00000337572.4

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58058 AN: 151856 Hom.: 11877 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.382 AC: 58120 AN: 151974 Hom.: 11893 Cov.: 31 AF XY: 0.388 AC XY: 28819 AN XY: 74286

African (AFR) AF: 0.492 AC: 20363 AN: 41424

American (AMR) AF: 0.434 AC: 6619 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3013 AN: 5170

South Asian (SAS) AF: 0.483 AC: 2323 AN: 4814

European-Finnish (FIN) AF: 0.275 AC: 2901 AN: 10568

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20066 AN: 67948

Other (OTH) AF: 0.422 AC: 892 AN: 2114

Alfa AF: 0.336 Hom.: 19087

Bravo AF: 0.399

Asia WGS AF: 0.519 AC: 1802 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.37
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1170101; hg19: chr13-42776055; COSMIC: COSV54940646;