Genetic Variant DIPK2B:p.Asp391His (chrX-45151783-C-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_176819.4(DIPK2B):c.1171G>C(p.Asp391His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,210,419 control chromosomes in the GnomAD database, including 1 homozygotes. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 8 hem., cov: 24)

Exomes 𝑓: 0.000094 ( 1 hom. 33 hem. )

Consequence

DIPK2B
NM_176819.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.668

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035396516).

BP6

Variant X-45151783-C-G is Benign according to our data. Variant chrX-45151783-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3054407.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4 link	c.1171G>C	p.Asp391His	missense_variant	Exon 5 of 5	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	XM_005272670.1 link	c.997G>C	p.Asp333His	missense_variant	Exon 4 of 4		XP_005272727.1
DIPK2B	XM_006724559.1 link	c.919G>C	p.Asp307His	missense_variant	Exon 4 of 4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7 link	c.1171G>C	p.Asp391His	missense_variant	Exon 5 of 5	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1
DIPK2B	ENST00000477281.1 link	n.469G>C		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.000205

AC:

AN:

112248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000941

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00536

Gnomad SAS

AF:

0.000367

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000281

AC:

AN:

181200

AF XY:

0.000252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00362

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000938

AC:

103

AN:

1098119

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

363553

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26402

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00301

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000923

AC:

AN:

54147

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

842031

Other (OTH)

AF:

0.000109

AC:

AN:

46081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000205

AC:

AN:

112300

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

34492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30954

American (AMR)

AF:

0.0000940

AC:

AN:

10637

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.00538

AC:

AN:

3533

South Asian (SAS)

AF:

0.000368

AC:

AN:

2720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53211

Other (OTH)

AF:

0.00

AC:

AN:

1536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.000340

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DIPK2B-related disorder

Benign:1

Jun 08, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

0.17

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

PhyloP100

0.67

PROVEAN

Benign

-1.3

REVEL

Benign

0.011

Sift

Uncertain

0.016

Sift4G

Uncertain

0.017

Vest4

0.030

MutPred

0.30

Loss of disorder (P = 0.0479);

MVP

0.30

MPC

0.57

ClinPred

0.021

GERP RS

1.8

gMVP

0.55

Mutation Taster

=99/1

polymorphism

(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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chrX-45151783-C-G

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