Genetic Variant NM_176819.4:c.383G>A (chrX-45191866-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_176819.4(DIPK2B):c.383G>A(p.Arg128Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,209,514 control chromosomes in the GnomAD database, including 54,780 homozygotes. There are 143,209 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.33 ( 4646 hom., 11095 hem., cov: 23)

Exomes 𝑓: 0.36 ( 50134 hom. 132114 hem. )

Consequence

DIPK2B
NM_176819.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.22

Publications

28 publications found

Variant links:

Genes affected

DIPK2B (HGNC:25866): (divergent protein kinase domain 2B) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

DIPK2B links:

ENSG00000229491 (HGNC:):

ENSG00000229491 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1131248E-6).

BP6

Variant X-45191866-C-T is Benign according to our data. Variant chrX-45191866-C-T is described in ClinVar as [Benign]. Clinvar id is 3059778.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4 link	c.383G>A	p.Arg128Lys	missense_variant	Exon 2 of 5	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	NM_024689.3 link	c.383G>A	p.Arg128Lys	missense_variant	Exon 2 of 3		NP_078965.2	Q9H7Y0-2
DIPK2B	XM_005272670.1 link	c.383G>A	p.Arg128Lys	missense_variant	Exon 2 of 4		XP_005272727.1
DIPK2B	XM_006724559.1 link	c.383G>A	p.Arg128Lys	missense_variant	Exon 2 of 4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7 link	c.383G>A	p.Arg128Lys	missense_variant	Exon 2 of 5	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

36274

AN:

111341

Hom.:

4647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.755

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.366

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.354

GnomAD2 exomes

AF:

0.423

AC:

77375

AN:

183077

AF XY:

0.419

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.597

Gnomad ASJ exome

AF:

0.421

Gnomad EAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.399

GnomAD4 exome

AF:

0.357

AC:

392210

AN:

1098118

Hom.:

50134

Cov.:

AF XY:

0.363

AC XY:

132114

AN XY:

363486

show subpopulations

African (AFR)

AF:

0.202

AC:

5335

AN:

26400

American (AMR)

AF:

0.578

AC:

20329

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

8142

AN:

19381

East Asian (EAS)

AF:

0.803

AC:

24239

AN:

30204

South Asian (SAS)

AF:

0.519

AC:

28117

AN:

54143

European-Finnish (FIN)

AF:

0.398

AC:

16132

AN:

40502

Middle Eastern (MID)

AF:

0.382

AC:

1580

AN:

4134

European-Non Finnish (NFE)

AF:

0.322

AC:

271089

AN:

842076

Other (OTH)

AF:

0.374

AC:

17247

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10183

20366

30550

40733

50916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.326

AC:

36290

AN:

111396

Hom.:

4646

Cov.:

AF XY:

0.330

AC XY:

11095

AN XY:

33616

show subpopulations

African (AFR)

AF:

0.202

AC:

6204

AN:

30714

American (AMR)

AF:

0.451

AC:

4766

AN:

10564

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1094

AN:

2643

East Asian (EAS)

AF:

0.756

AC:

2631

AN:

3479

South Asian (SAS)

AF:

0.523

AC:

1390

AN:

2658

European-Finnish (FIN)

AF:

0.380

AC:

2270

AN:

5972

Middle Eastern (MID)

AF:

0.359

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.326

AC:

17251

AN:

52939

Other (OTH)

AF:

0.358

AC:

547

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

846

1692

2537

3383

4229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.341

Hom.:

42796

Bravo

AF:

0.332

TwinsUK

AF:

0.319

AC:

1181

ALSPAC

AF:

0.317

AC:

915

ESP6500AA

AF:

0.202

AC:

774

ESP6500EA

AF:

0.325

AC:

2185

ExAC

AF:

0.411

AC:

49870

EpiCase

AF:

0.326

EpiControl

AF:

0.326

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DIPK2B-related disorder

Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.082

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.96

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0000021

T;T

MetaSVM

Benign

-0.95

PhyloP100

1.2

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.018

Sift

Benign

0.67

T;T

Sift4G

Benign

0.73

T;T

Vest4

0.027

MPC

0.23

ClinPred

0.0027

GERP RS

2.9

gMVP

0.66

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_176819.4:c.383G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over