Variant chr12-55939426-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001351038.2(DGKA):c.-368C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,614,116 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 58 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 47 hom. )

Consequence

DGKA
NM_001351038.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.09

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 12-55939426-C-T is Benign according to our data. Variant chr12-55939426-C-T is described in ClinVar as [Benign]. Clinvar id is 715651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2107/152234) while in subpopulation AFR AF= 0.0451 (1875/41532). AF 95% confidence interval is 0.0434. There are 58 homozygotes in gnomad4. There are 1003 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2107 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKA	NM_001345.5 linkuse as main transcript	c.606C>T	p.Asp202Asp	synonymous_variant	9/24	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.606C>T	p.Asp202Asp	synonymous_variant	9/24	5	NM_001345.5	ENSP00000328405.5		P23743-1

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2107

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0453

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.00465

AC:

1170

AN:

251402

Hom.:

AF XY:

0.00372

AC XY:

505

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0460

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.000413

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00182

AC:

2657

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1191

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0472

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000951

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

AF:

0.0138

AC:

2107

AN:

152234

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1003

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0451

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00368

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 09, 2018	- -

DGKA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 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

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.5

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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