Genetic Variant DIPK2B:p.Arg143Leu (chrX-45191821-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_176819.4(DIPK2B):c.428G>T(p.Arg143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,210,636 control chromosomes in the GnomAD database, including 17 homozygotes. There are 391 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., 43 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 14 hom. 348 hem. )

Consequence

DIPK2B
NM_176819.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.646

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004731655).

BP6

Variant X-45191821-C-A is Benign according to our data. Variant chrX-45191821-C-A is described in ClinVar as [Benign]. Clinvar id is 3033826.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00112 (1229/1098049) while in subpopulation AMR AF= 0.0307 (1081/35204). AF 95% confidence interval is 0.0292. There are 14 homozygotes in gnomad4_exome. There are 348 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4 link	c.428G>T	p.Arg143Leu	missense_variant	Exon 2 of 5	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	NM_024689.3 link	c.428G>T	p.Arg143Leu	missense_variant	Exon 2 of 3		NP_078965.2	Q9H7Y0-2
DIPK2B	XM_005272670.1 link	c.428G>T	p.Arg143Leu	missense_variant	Exon 2 of 4		XP_005272727.1
DIPK2B	XM_006724559.1 link	c.428G>T	p.Arg143Leu	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.428G>T	p.Arg143Leu	missense_variant	Exon 2 of 5	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

173

AN:

112534

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

34680

show subpopulations

Gnomad AFR

AF:

0.000388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00140

Gnomad SAS

AF:

0.000735

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00395

GnomAD3 exomes

AF:

0.00493

AC:

903

AN:

183149

Hom.:

AF XY:

0.00349

AC XY:

236

AN XY:

67619

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.0311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00231

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00112

AC:

1229

AN:

1098049

Hom.:

Cov.:

AF XY:

0.000958

AC XY:

348

AN XY:

363405

show subpopulations

Gnomad4 AFR exome

AF:

0.000417

Gnomad4 AMR exome

AF:

0.0307

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00182

Gnomad4 SAS exome

AF:

0.000148

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000226

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00155

AC:

174

AN:

112587

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

34743

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00140

Gnomad4 SAS

AF:

0.000737

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00390

Alfa

AF:

0.000254

Hom.:

Bravo

AF:

0.00323

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00330

AC:

401

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DIPK2B-related disorder

Benign:1

Oct 01, 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

0.18

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.88

D;D

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.91

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.13

Sift

Benign

0.077

T;D

Sift4G

Benign

0.16

T;T

Vest4

0.14

MVP

0.55

MPC

0.52

ClinPred

0.031

GERP RS

3.0

gMVP

0.68

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