Genetic Variant DIPK2B:c.499-4G>T (chrX-45157892-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_176819.4(DIPK2B):c.499-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000479 in 1,085,654 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., 1 hem., cov: 19)

Exomes 𝑓: 0.000049 ( 0 hom. 14 hem. )

Consequence

DIPK2B
NM_176819.4 splice_region, intron

Scores

Splicing: ADA: 0.00001843

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.44

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-45157892-C-A is Benign according to our data. Variant chrX-45157892-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2660376.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 14 gene

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.499-4G>T		splice_region intron	N/A	NP_789789.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DIPK2B	ENST00000398000.7	TSL:5 MANE Select	c.499-4G>T	splice_region intron	N/A	ENSP00000381086.2	Q9H7Y0-1
DIPK2B	ENST00000905163.1		c.499-40G>T	intron	N/A	ENSP00000575222.1
DIPK2B	ENST00000905164.1		c.499-3694G>T	intron	N/A	ENSP00000575223.1

Frequencies

GnomAD3 genomes

AF:

0.0000390

AC:

AN:

102514

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000795

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000103

AC:

AN:

97149

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:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000488

AC:

AN:

983140

Hom.:

Cov.:

AF XY:

0.0000464

AC XY:

AN XY:

301656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23298

American (AMR)

AF:

0.00

AC:

AN:

25949

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16572

East Asian (EAS)

AF:

0.00

AC:

AN:

23199

South Asian (SAS)

AF:

0.00

AC:

AN:

46098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2559

European-Non Finnish (NFE)

AF:

0.0000555

AC:

AN:

774300

Other (OTH)

AF:

0.000124

AC:

AN:

40219

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000390

AC:

AN:

102514

Hom.:

Cov.:

AF XY:

0.0000380

AC XY:

AN XY:

26306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28102

American (AMR)

AF:

0.00

AC:

AN:

9375

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2518

East Asian (EAS)

AF:

0.00

AC:

AN:

3119

South Asian (SAS)

AF:

0.00

AC:

AN:

2074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4817

Middle Eastern (MID)

AF:

0.00

AC:

AN:

223

European-Non Finnish (NFE)

AF:

0.0000795

AC:

AN:

50306

Other (OTH)

AF:

0.00

AC:

AN:

1352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.014

(source)

DANN

Benign

0.46

PhyloP100

-2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over