Variant 12-55940401-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.886A>G(p.Thr296Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,614,204 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 13 hom. )

Consequence

DGKA
NM_001345.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.50

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=0.013282895).

BP6

Variant 12-55940401-A-G is Benign according to our data. Variant chr12-55940401-A-G is described in ClinVar as [Benign]. Clinvar id is 3040632.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 455 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKA	NM_001345.5 linkuse as main transcript	c.886A>G	p.Thr296Ala	missense_variant	11/24	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.886A>G	p.Thr296Ala	missense_variant	11/24	5	NM_001345.5	ENSP00000328405.5		P23743-1

Frequencies

GnomAD3 genomes

AF:

0.00299

AC:

455

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00979

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00442

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00291

AC:

731

AN:

251454

Hom.:

AF XY:

0.00274

AC XY:

372

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00371

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00408

AC:

5968

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

2954

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.00931

Gnomad4 NFE exome

AF:

0.00461

Gnomad4 OTH exome

AF:

0.00298

GnomAD4 genome

AF:

0.00299

AC:

455

AN:

152326

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

234

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00979

Gnomad4 NFE

AF:

0.00442

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00205

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00291

AC:

353

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00273

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DGKA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 2019

This variant is classified as 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

0.068

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Uncertain

0.59

D;.;D;D

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.82

.;T;T;.

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Uncertain

-0.035

MutationAssessor

Benign

1.4

L;.;L;L

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.8

D;D;D;D

REVEL

Benign

0.27

Sift

Benign

0.079

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.032

B;B;B;B

Vest4

0.095

MVP

0.82

MPC

0.57

ClinPred

0.035

GERP RS

4.0

Varity_R

0.21

gMVP

0.55

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

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