2-233354615-C-T

Variant names:

• chr2-233354615-C-T
• rs867873568
• NM_152879.3:c.97C>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.97C>T​(p.Pro33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000222 in 1,128,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P33L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: DGKD NM_152879.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• 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=0.2503913).

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.97C>T	p.Pro33Ser	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.97C>T	p.Pro33Ser	missense	Exon 1 of 30	ENSP00000264057.2	Q16760-1
	DGKD	ENST00000963810.1		c.97C>T	p.Pro33Ser	missense	Exon 1 of 31	ENSP00000633869.1
	DGKD	ENST00000963809.1		c.97C>T	p.Pro33Ser	missense	Exon 1 of 31	ENSP00000633868.1

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 146120 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: 0.00

Gnomad NFE AF: 0.0000304

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000234 AC: 23 AN: 982500 Hom.: 0 Cov.: 31 AF XY: 0.0000188 AC XY: 9 AN XY: 477814

African (AFR) AF: 0.00 AC: 0 AN: 19202

American (AMR) AF: 0.00 AC: 0 AN: 16244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12106

East Asian (EAS) AF: 0.00 AC: 0 AN: 6462

South Asian (SAS) AF: 0.00 AC: 0 AN: 47334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2612

European-Non Finnish (NFE) AF: 0.0000250 AC: 21 AN: 838752

Other (OTH) AF: 0.0000600 AC: 2 AN: 33348

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 146120 Hom.: 0 Cov.: 30 AF XY: 0.0000141 AC XY: 1 AN XY: 71040

African (AFR) AF: 0.00 AC: 0 AN: 40782

American (AMR) AF: 0.00 AC: 0 AN: 14754

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5038

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000304 AC: 2 AN: 65718

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

Alfa AF: 0.00 Hom.: 0

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	0.11
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.28	N
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	0.81	L
PhyloP100		1.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.050	T
Polyphen		0.98	D
Vest4		0.14
MutPred		0.20		Gain of phosphorylation at P33 (P = 0.0031)
MVP		0.77
MPC		0.50
ClinPred		0.63	D
GERP RS		1.3
PromoterAI		0.040	Neutral
Varity_R		0.086
gMVP		0.43
Mutation Taster		=76/24	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: rs867873568; hg19: chr2-234263261;