Genetic Variant DIPK2B:p.Arg143Pro (chrX-45191821-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_176819.4(DIPK2B):c.428G>C(p.Arg143Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 112,587 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R143L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

DIPK2B
NM_176819.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.646

Publications

1 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06933278).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176819.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIPK2B	NM_176819.4	MANE Select	c.428G>C	p.Arg143Pro	missense	Exon 2 of 5	NP_789789.2
	DIPK2B	NM_024689.3		c.428G>C	p.Arg143Pro	missense	Exon 2 of 3	NP_078965.2	Q9H7Y0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DIPK2B	ENST00000398000.7	TSL:5 MANE Select	c.428G>C	p.Arg143Pro	missense	Exon 2 of 5	ENSP00000381086.2	Q9H7Y0-1
DIPK2B	ENST00000377934.4	TSL:1	c.428G>C	p.Arg143Pro	missense	Exon 2 of 3	ENSP00000367168.4	Q9H7Y0-2
DIPK2B	ENST00000905163.1		c.428G>C	p.Arg143Pro	missense	Exon 2 of 5	ENSP00000575222.1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000735

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183149

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.11e-7

AC:

AN:

1098049

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363405

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26399

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54139

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841996

Other (OTH)

AF:

0.00

AC:

AN:

46095

Age Distribution

Exome Hom

Variant carriers

<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:

0.0000178

AC:

AN:

112587

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34743

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31010

American (AMR)

AF:

0.00

AC:

AN:

10705

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3571

South Asian (SAS)

AF:

0.000737

AC:

AN:

2714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53303

Other (OTH)

AF:

0.00

AC:

AN:

1538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.97

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.85

M_CAP

Benign

0.028

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.69

PhyloP100

0.65

PROVEAN

Benign

-2.1

REVEL

Benign

0.17

Sift

Benign

0.061

Sift4G

Benign

0.11

Vest4

0.33

MutPred

0.32

Loss of MoRF binding (P = 8e-04)

MVP

0.55

MPC

0.88

ClinPred

0.67

GERP RS

3.0

gMVP

0.88

Mutation Taster

=79/21

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over