Genetic Variant DIPK2B:c.499-4G>A (chrX-45157892-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_176819.4(DIPK2B):c.499-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,085,656 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000078 ( 0 hom., 2 hem., cov: 19)

Exomes 𝑓: 0.0000051 ( 0 hom. 4 hem. )

Consequence

DIPK2B
NM_176819.4 splice_region, intron

Scores

Splicing: ADA: 0.00001838

Clinical Significance

Not reported in ClinVar

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS2

High Hemizygotes in GnomAd4 at 2 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>A		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>A	splice_region intron	N/A	ENSP00000381086.2	Q9H7Y0-1
DIPK2B	ENST00000905163.1		c.499-40G>A	intron	N/A	ENSP00000575222.1
DIPK2B	ENST00000905164.1		c.499-3694G>A	intron	N/A	ENSP00000575223.1

Frequencies

GnomAD3 genomes

AF:

0.0000780

AC:

AN:

102514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000285

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000103

AC:

AN:

97149

AF XY:

0.0000336

show subpopulations

Gnomad AFR exome

AF:

0.000184

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

AF:

0.00000509

AC:

AN:

983142

Hom.:

Cov.:

AF XY:

0.0000133

AC XY:

AN XY:

301658

show subpopulations

African (AFR)

AF:

0.000129

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:

23200

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:

0.00000129

AC:

AN:

774301

Other (OTH)

AF:

0.0000249

AC:

AN:

40219

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.0000780

AC:

AN:

102514

Hom.:

Cov.:

AF XY:

0.0000760

AC XY:

AN XY:

26306

show subpopulations

African (AFR)

AF:

0.000285

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:

0.00

AC:

AN:

50306

Other (OTH)

AF:

0.00

AC:

AN:

1352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.016

(source)

DANN

Benign

0.52

PhyloP100

-2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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