dbSNP rs201256036: DIPK2B:p.Leu366Leu (chrX-45151858-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_176819.4(DIPK2B):c.1096C>T(p.Leu366Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,209,973 control chromosomes in the GnomAD database, including 1 homozygotes. There are 74 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 44 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 1 hom. 30 hem. )

Consequence

DIPK2B
NM_176819.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.90

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-45151858-G-A is Benign according to our data. Variant chrX-45151858-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050838.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.9 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 44 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4 link	c.1096C>T	p.Leu366Leu	synonymous_variant	Exon 5 of 5	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	XM_005272670.1 link	c.922C>T	p.Leu308Leu	synonymous_variant	Exon 4 of 4		XP_005272727.1
DIPK2B	XM_006724559.1 link	c.844C>T	p.Leu282Leu	synonymous_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.1096C>T	p.Leu366Leu	synonymous_variant	Exon 5 of 5	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1
DIPK2B	ENST00000477281.1 link	n.394C>T		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

150

AN:

112688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000280

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:

0.0000188

Gnomad OTH

AF:

0.00131

GnomAD2 exomes

AF:

0.000303

AC:

AN:

178303

AF XY:

0.000139

show subpopulations

Gnomad AFR exome

AF:

0.00396

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000126

Gnomad OTH exome

AF:

0.000453

GnomAD4 exome

AF:

0.000126

AC:

138

AN:

1097231

Hom.:

Cov.:

AF XY:

0.0000827

AC XY:

AN XY:

362705

show subpopulations

African (AFR)

AF:

0.00451

AC:

119

AN:

26391

American (AMR)

AF:

0.0000570

AC:

AN:

35115

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19365

East Asian (EAS)

AF:

0.00

AC:

AN:

30184

South Asian (SAS)

AF:

0.00

AC:

AN:

53949

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40480

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841557

Other (OTH)

AF:

0.000326

AC:

AN:

46053

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00134

AC:

151

AN:

112742

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

34904

show subpopulations

African (AFR)

AF:

0.00466

AC:

145

AN:

31084

American (AMR)

AF:

0.000279

AC:

AN:

10736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2739

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53263

Other (OTH)

AF:

0.00129

AC:

AN:

1546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000825

Hom.:

Bravo

AF:

0.00153

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DIPK2B-related disorder

Benign:1

Jul 11, 2019

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.8

(source)

DANN

Benign

0.76

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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rs201256036

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