Variant X-45191866-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

DIPK2B (HGNC:):

DIPK2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DIPK2B	NM_176819.4 linkuse as main transcript	c.383G>A	p.Arg128Lys	missense_variant	2/5	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	NM_024689.3 linkuse as main transcript	c.383G>A	p.Arg128Lys	missense_variant	2/3		NP_078965.2	Q9H7Y0-2
DIPK2B	XM_005272670.1 linkuse as main transcript	c.383G>A	p.Arg128Lys	missense_variant	2/4		XP_005272727.1
DIPK2B	XM_006724559.1 linkuse as main transcript	c.383G>A	p.Arg128Lys	missense_variant	2/4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7 linkuse as main transcript	c.383G>A	p.Arg128Lys	missense_variant	2/5	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

36274

AN:

111341

Hom.:

4647

Cov.:

AF XY:

0.330

AC XY:

11069

AN XY:

33551

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

GnomAD3 exomes

AF:

0.423

AC:

77375

AN:

183077

Hom.:

11752

AF XY:

0.419

AC XY:

28316

AN XY:

67533

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 SAS exome

AF:

0.526

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

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.578

Gnomad4 ASJ exome

AF:

0.420

Gnomad4 EAS exome

AF:

0.803

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.398

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.326

AC:

36290

AN:

111396

Hom.:

4646

Cov.:

AF XY:

0.330

AC XY:

11095

AN XY:

33616

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.451

Gnomad4 ASJ

AF:

0.414

Gnomad4 EAS

AF:

0.756

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.326

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.347

Hom.:

36340

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 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

0.082

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

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

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

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

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