2-233354616-C-T

Variant names:

• chr2-233354616-C-T
• rs750944437
• NM_152879.3:c.98C>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.98C>T​(p.Pro33Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,129,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P33S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: DGKD NM_152879.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0300
• Publications: 1 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=0.16455957).

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.98C>T	p.Pro33Leu	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.98C>T	p.Pro33Leu	missense	Exon 1 of 30	ENSP00000264057.2	Q16760-1
	DGKD	ENST00000963810.1		c.98C>T	p.Pro33Leu	missense	Exon 1 of 31	ENSP00000633869.1
	DGKD	ENST00000963809.1		c.98C>T	p.Pro33Leu	missense	Exon 1 of 31	ENSP00000633868.1

Frequencies

GnomAD3 genomes AF: 0.0000821 AC: 12 AN: 146102 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000678

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000137

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000568 AC: 5 AN: 88028 AF XY: 0.0000582

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000394

Gnomad NFE exome AF: 0.0000773

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000106 AC: 104 AN: 982914 Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 52 AN XY: 478084

African (AFR) AF: 0.0000520 AC: 1 AN: 19228

American (AMR) AF: 0.00 AC: 0 AN: 16290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12102

East Asian (EAS) AF: 0.00 AC: 0 AN: 6490

South Asian (SAS) AF: 0.00 AC: 0 AN: 47378

European-Finnish (FIN) AF: 0.000155 AC: 1 AN: 6460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2626

European-Non Finnish (NFE) AF: 0.000114 AC: 96 AN: 838986

Other (OTH) AF: 0.000180 AC: 6 AN: 33354

GnomAD4 genome AF: 0.0000821 AC: 12 AN: 146102 Hom.: 0 Cov.: 30 AF XY: 0.0000422 AC XY: 3 AN XY: 71040

African (AFR) AF: 0.0000490 AC: 2 AN: 40782

American (AMR) AF: 0.0000678 AC: 1 AN: 14746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000137 AC: 9 AN: 65708

Other (OTH) AF: 0.00 AC: 0 AN: 2008

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000375 AC: 4

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	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.20	N
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	0.81	L
PhyloP100		-0.030
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.12
MutPred		0.23		Loss of loop (P = 9e-04)
MVP		0.76
MPC		0.50
ClinPred		0.11	T
GERP RS		1.3
PromoterAI		0.024	Neutral
Varity_R		0.084
gMVP		0.43
Mutation Taster		=79/21	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: rs750944437; hg19: chr2-234263262;