NM_001350709.2:c.2122+18131G>A

Variant names:

• chr7-14320384-C-T
• rs10215596
• NM_001350709.2:c.2122+18131G>A

Variant summary

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

The NM_001350709.2(DGKB):​c.2122+18131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 152,148 control chromosomes in the GnomAD database, including 633 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 0.086 (633 hom., cov: 32)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 2 publications found

Genes affected

DGKB (HGNC:2850): (diacylglycerol kinase beta) Diacylglycerol kinases (DGKs) are regulators of the intracellular concentration of the second messenger diacylglycerol (DAG) and thus play a key role in cellular processes. Nine mammalian isotypes have been identified, which are encoded by separate genes. Mammalian DGK isozymes contain a conserved catalytic (kinase) domain and a cysteine-rich domain (CRD). The protein encoded by this gene is a diacylglycerol kinase, beta isotype. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.2122+18131G>A		intron_variant	Intron 23 of 25	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.2122+18131G>A		intron_variant	Intron 23 of 25	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13156 AN: 152030 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0748

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0699

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

GnomAD4 genome AF: 0.0865 AC: 13156 AN: 152148 Hom.: 633 Cov.: 32 AF XY: 0.0881 AC XY: 6550 AN XY: 74372

African (AFR) AF: 0.0552 AC: 2293 AN: 41524

American (AMR) AF: 0.0747 AC: 1142 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.139 AC: 715 AN: 5146

South Asian (SAS) AF: 0.119 AC: 573 AN: 4818

European-Finnish (FIN) AF: 0.0993 AC: 1053 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6834 AN: 67992

Other (OTH) AF: 0.0692 AC: 146 AN: 2110

Alfa AF: 0.0860 Hom.: 805

Bravo AF: 0.0790

Asia WGS AF: 0.143 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.53
PhyloP100		-0.41
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: rs10215596; hg19: chr7-14360009;