Genetic Variant DIPK2B:p.Lys364Lys (chrX-45151862-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_176819.4(DIPK2B):c.1092G>A(p.Lys364Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000788 in 1,210,112 control chromosomes in the GnomAD database, including 3 homozygotes. There are 248 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., 123 hem., cov: 24)

Exomes 𝑓: 0.00048 ( 1 hom. 125 hem. )

Consequence

DIPK2B
NM_176819.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00500

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant X-45151862-C-T is Benign according to our data. Variant chrX-45151862-C-T is described in ClinVar as Benign. ClinVar VariationId is 711138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.005 with no splicing effect.

BS2

High Homozygotes 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.1092G>A	p.Lys364Lys	synonymous	Exon 5 of 5	NP_789789.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DIPK2B	ENST00000398000.7	TSL:5 MANE Select	c.1092G>A	p.Lys364Lys	synonymous	Exon 5 of 5	ENSP00000381086.2	Q9H7Y0-1
DIPK2B	ENST00000905163.1		c.1056G>A	p.Lys352Lys	synonymous	Exon 5 of 5	ENSP00000575222.1
DIPK2B	ENST00000905164.1		c.918G>A	p.Lys306Lys	synonymous	Exon 4 of 4	ENSP00000575223.1

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

422

AN:

112729

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000745

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:

0.0000375

Gnomad OTH

AF:

0.000655

GnomAD2 exomes

AF:

0.000915

AC:

163

AN:

178099

AF XY:

0.000618

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.000552

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000149

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000481

AC:

528

AN:

1097330

Hom.:

Cov.:

AF XY:

0.000345

AC XY:

125

AN XY:

362802

show subpopulations

African (AFR)

AF:

0.0138

AC:

363

AN:

26392

American (AMR)

AF:

0.000541

AC:

AN:

35123

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19371

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30186

South Asian (SAS)

AF:

0.0000371

AC:

AN:

53966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40479

Middle Eastern (MID)

AF:

0.00242

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.000111

AC:

AN:

841623

Other (OTH)

AF:

0.000869

AC:

AN:

46053

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00377

AC:

425

AN:

112782

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

123

AN XY:

34934

show subpopulations

African (AFR)

AF:

0.0133

AC:

414

AN:

31106

American (AMR)

AF:

0.000745

AC:

AN:

10745

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3570

South Asian (SAS)

AF:

0.00

AC:

AN:

2723

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6265

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000375

AC:

AN:

53269

Other (OTH)

AF:

0.000647

AC:

AN:

1546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000348

Hom.:

Bravo

AF:

0.00404

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

DIPK2B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.5

(source)

DANN

Benign

0.69

PhyloP100

0.0050

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over