Genetic Variant DIPK2B:p.Ala328Ala (chrX-45151970-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_176819.4(DIPK2B):c.984A>G(p.Ala328Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,176,326 control chromosomes in the GnomAD database, including 1 homozygotes. There are 47 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 1 hom., 22 hem., cov: 24)

Exomes 𝑓: 0.000089 ( 0 hom. 25 hem. )

Consequence

DIPK2B
NM_176819.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.534

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-45151970-T-C is Benign according to our data. Variant chrX-45151970-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 712302.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.534 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4 link	c.984A>G	p.Ala328Ala	synonymous_variant	Exon 5 of 5	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	XM_005272670.1 link	c.810A>G	p.Ala270Ala	synonymous_variant	Exon 4 of 4		XP_005272727.1
DIPK2B	XM_006724559.1 link	c.732A>G	p.Ala244Ala	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.984A>G	p.Ala328Ala	synonymous_variant	Exon 5 of 5	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1
DIPK2B	ENST00000477281.1 link	n.282A>G		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.000807

AC:

AN:

112735

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00293

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:

0.000192

AC:

AN:

125041

AF XY:

0.000176

show subpopulations

Gnomad AFR exome

AF:

0.00294

Gnomad AMR exome

AF:

0.0000482

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:

0.0000893

AC:

AN:

1063591

Hom.:

Cov.:

AF XY:

0.0000725

AC XY:

AN XY:

344605

show subpopulations

African (AFR)

AF:

0.00318

AC:

AN:

25445

American (AMR)

AF:

0.000101

AC:

AN:

29676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18684

East Asian (EAS)

AF:

0.00

AC:

AN:

28212

South Asian (SAS)

AF:

0.00

AC:

AN:

50315

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38473

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4082

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

823977

Other (OTH)

AF:

0.000224

AC:

AN:

44727

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000807

AC:

AN:

112735

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

34891

show subpopulations

African (AFR)

AF:

0.00293

AC:

AN:

31036

American (AMR)

AF:

0.00

AC:

AN:

10725

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3573

South Asian (SAS)

AF:

0.00

AC:

AN:

2758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53326

Other (OTH)

AF:

0.00

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.000873

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.74

(source)

DANN

Benign

0.42

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

X-45151970-T-C

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