Genetic Variant NM_001345.5:c.1175+41G>A (chr12-55941366-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001345.5(DGKA):c.1175+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,602,570 control chromosomes in the GnomAD database, including 66,656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4376 hom., cov: 31)

Exomes 𝑓: 0.29 ( 62280 hom. )

Consequence

DGKA
NM_001345.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

Publications

14 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKA	NM_001345.5 link	c.1175+41G>A		intron_variant	Intron 14 of 23	ENST00000331886.10	NP_001336.2	P23743-1A0A024RB23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKA	ENST00000331886.10 link	c.1175+41G>A		intron_variant	Intron 14 of 23	5	NM_001345.5	ENSP00000328405.5		P23743-1

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32495

AN:

151946

Hom.:

4379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.217

GnomAD2 exomes

AF:

0.265

AC:

65938

AN:

248914

AF XY:

0.280

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.315

Gnomad EAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.287

AC:

416622

AN:

1450506

Hom.:

62280

Cov.:

AF XY:

0.292

AC XY:

210693

AN XY:

720776

show subpopulations

African (AFR)

AF:

0.0440

AC:

1464

AN:

33254

American (AMR)

AF:

0.166

AC:

7388

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

8158

AN:

25888

East Asian (EAS)

AF:

0.279

AC:

11024

AN:

39518

South Asian (SAS)

AF:

0.395

AC:

33891

AN:

85744

European-Finnish (FIN)

AF:

0.235

AC:

12537

AN:

53274

Middle Eastern (MID)

AF:

0.281

AC:

1610

AN:

5732

European-Non Finnish (NFE)

AF:

0.293

AC:

323584

AN:

1102688

Other (OTH)

AF:

0.283

AC:

16966

AN:

59908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

14849

29698

44547

59396

74245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10744

21488

32232

42976

53720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.214

AC:

32474

AN:

152064

Hom.:

4376

Cov.:

AF XY:

0.213

AC XY:

15795

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0537

AC:

2230

AN:

41502

American (AMR)

AF:

0.190

AC:

2896

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1120

AN:

3470

East Asian (EAS)

AF:

0.282

AC:

1455

AN:

5168

South Asian (SAS)

AF:

0.395

AC:

1906

AN:

4820

European-Finnish (FIN)

AF:

0.233

AC:

2459

AN:

10554

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19657

AN:

67960

Other (OTH)

AF:

0.216

AC:

456

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1183

2366

3550

4733

5916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.253

Hom.:

2620

Bravo

AF:

0.201

Asia WGS

AF:

0.355

AC:

1236

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.1

PromoterAI

-0.042

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over