Variant 12-55938925-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001345.5(DGKA):c.410A>G(p.Lys137Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,614,228 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 7 hom. )

Consequence

DGKA
NM_001345.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.50

Variant links:

Genes affected

DGKA (HGNC:2849): (diacylglycerol kinase alpha) The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and phosphorylating diacylglycerol to phosphatidic acid. Several transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2017]

DGKA links:

DGKA (HGNC:):

DGKA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004499942).

BP6

Variant 12-55938925-A-G is Benign according to our data. Variant chr12-55938925-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042893.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKA	NM_001345.5 linkuse as main transcript	c.410A>G	p.Lys137Arg	missense_variant	7/24	ENST00000331886.10	NP_001336.2	P23743-1A0A024RB23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKA	ENST00000331886.10 linkuse as main transcript	c.410A>G	p.Lys137Arg	missense_variant	7/24	5	NM_001345.5	ENSP00000328405.5		P23743-1

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00213

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00176

AC:

443

AN:

251486

Hom.:

AF XY:

0.00181

AC XY:

246

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00251

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00190

AC:

2782

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1377

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00211

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00140

AC:

213

AN:

152334

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00213

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00165

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00164

AC:

199

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00290

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DGKA-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.036

T;.;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.82

.;T;T;T;.

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0045

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.32

N;.;.;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.71

N;N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.67

T;T;T;T;T

Sift4G

Benign

0.69

T;T;T;T;T

Polyphen

0.0

B;B;.;B;B

Vest4

0.11

MVP

0.61

MPC

0.45

ClinPred

0.00089

GERP RS

-4.4

Varity_R

0.084

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over