chr2-233354546-C-G

Variant names:

• chr2-233354546-C-G
• rs1229827757
• NM_152879.3:c.28C>G

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.28C>G​(p.Pro10Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 145,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P10L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DGKD NM_152879.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35
• 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=0.14017758).

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.28C>G	p.Pro10Ala	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.28C>G	p.Pro10Ala	missense	Exon 1 of 30	ENSP00000264057.2	Q16760-1
	DGKD	ENST00000963810.1		c.28C>G	p.Pro10Ala	missense	Exon 1 of 31	ENSP00000633869.1
	DGKD	ENST00000963809.1		c.28C>G	p.Pro10Ala	missense	Exon 1 of 31	ENSP00000633868.1

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 145652 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000491

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 867294 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 408588

African (AFR) AF: 0.00 AC: 0 AN: 16184

American (AMR) AF: 0.00 AC: 0 AN: 2090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5952

East Asian (EAS) AF: 0.00 AC: 0 AN: 4264

South Asian (SAS) AF: 0.00 AC: 0 AN: 24022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 783054

Other (OTH) AF: 0.00 AC: 0 AN: 28516

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 145652 Hom.: 0 Cov.: 30 AF XY: 0.0000282 AC XY: 2 AN XY: 70798

African (AFR) AF: 0.0000491 AC: 2 AN: 40710

American (AMR) AF: 0.00 AC: 0 AN: 14708

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4992

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65528

Other (OTH) AF: 0.00 AC: 0 AN: 2004

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.047
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.73
DEOGEN2	Benign	0.074	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.061	N
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.080	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.23
Sift	Benign	0.25	T
Sift4G	Benign	0.42	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.19		Loss of glycosylation at P10 (P = 0.0035)
MVP		0.54
MPC		0.48
ClinPred		0.049	T
GERP RS		-1.2
PromoterAI		-0.037	Neutral
Varity_R		0.045
gMVP		0.37
Mutation Taster		=90/10	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: rs1229827757; hg19: chr2-234263192;