chr2-233354541-C-T

Variant names:

• chr2-233354541-C-T
• rs1260799159
• NM_152879.3:c.23C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152879.3(DGKD):​c.23C>T​(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,002,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P8P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: DGKD NM_152879.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.751
• Publications: 0 publications found

Genes affected

DGKD (HGNC:2851): (diacylglycerol kinase delta) This gene encodes a cytoplasmic enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. Diacylglycerol and phosphatidic acid are two lipids that act as second messengers in signaling cascades. Their cellular concentrations are regulated by the encoded protein, and so it is thought to play an important role in cellular signal transduction. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14228356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152879.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKD	NM_152879.3	MANE Select	c.23C>T	p.Pro8Leu	missense	Exon 1 of 30	NP_690618.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKD	ENST00000264057.7	TSL:1 MANE Select	c.23C>T	p.Pro8Leu	missense	Exon 1 of 30	ENSP00000264057.2	Q16760-1
	DGKD	ENST00000963810.1		c.23C>T	p.Pro8Leu	missense	Exon 1 of 31	ENSP00000633869.1
	DGKD	ENST00000963809.1		c.23C>T	p.Pro8Leu	missense	Exon 1 of 31	ENSP00000633868.1

Frequencies

GnomAD3 genomes AF: 0.0000206 AC: 3 AN: 145698 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.0000305

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000210 AC: 18 AN: 856864 Hom.: 0 Cov.: 30 AF XY: 0.0000224 AC XY: 9 AN XY: 401482

African (AFR) AF: 0.0000624 AC: 1 AN: 16024

American (AMR) AF: 0.00 AC: 0 AN: 1408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5540

East Asian (EAS) AF: 0.00 AC: 0 AN: 4150

South Asian (SAS) AF: 0.00 AC: 0 AN: 21662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1720

European-Non Finnish (NFE) AF: 0.0000193 AC: 15 AN: 777256

Other (OTH) AF: 0.0000712 AC: 2 AN: 28090

GnomAD4 genome AF: 0.0000206 AC: 3 AN: 145724 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 70876

African (AFR) AF: 0.00 AC: 0 AN: 40792

American (AMR) AF: 0.00 AC: 0 AN: 14730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4970

South Asian (SAS) AF: 0.00 AC: 0 AN: 4776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8306

Middle Eastern (MID) AF: 0.00357 AC: 1 AN: 280

European-Non Finnish (NFE) AF: 0.0000305 AC: 2 AN: 65554

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.038	N
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.75
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.080	N
REVEL	Benign	0.18
Sift	Benign	0.26	T
Sift4G	Benign	0.16	T
Polyphen		0.0070	B
Vest4		0.12
MutPred		0.20		Loss of glycosylation at P8 (P = 0.0125)
MVP		0.42
MPC		0.50
ClinPred		0.063	T
GERP RS		0.40
PromoterAI		0.52	Over-expression
Varity_R		0.056
gMVP		0.34
Mutation Taster		=95/5	polymorphism

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: rs1260799159; hg19: chr2-234263187;