Genetic Variant NM_176819.4:c.313T>C (chrX-45191936-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_176819.4(DIPK2B):c.313T>C(p.Ser105Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,210,312 control chromosomes in the GnomAD database, including 6 homozygotes. There are 568 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., 24 hem., cov: 23)

Exomes 𝑓: 0.00092 ( 6 hom. 544 hem. )

Consequence

DIPK2B
NM_176819.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.867

Publications

2 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:

ENSG00000229491 (HGNC:):

ENSG00000229491 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007990241).

BP6

Variant X-45191936-A-G is Benign according to our data. Variant chrX-45191936-A-G is described in ClinVar as [Benign]. Clinvar id is 3046016.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4 link	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 5	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	NM_024689.3 link	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 3		NP_078965.2	Q9H7Y0-2
DIPK2B	XM_005272670.1 link	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 4		XP_005272727.1
DIPK2B	XM_006724559.1 link	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7 link	c.313T>C	p.Ser105Pro	missense_variant	Exon 2 of 5	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1

Frequencies

GnomAD3 genomes

AF:

0.000490

AC:

AN:

112186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000188

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00997

Gnomad FIN

AF:

0.000487

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.000394

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00154

AC:

283

AN:

183232

AF XY:

0.00253

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.0000722

Gnomad FIN exome

AF:

0.000376

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000924

AC:

1015

AN:

1098073

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

544

AN XY:

363427

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26401

American (AMR)

AF:

0.0000852

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.000310

AC:

AN:

19384

East Asian (EAS)

AF:

0.0000662

AC:

AN:

30205

South Asian (SAS)

AF:

0.0126

AC:

682

AN:

54137

European-Finnish (FIN)

AF:

0.000395

AC:

AN:

40528

Middle Eastern (MID)

AF:

0.00290

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.000295

AC:

248

AN:

841984

Other (OTH)

AF:

0.000976

AC:

AN:

46091

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000499

AC:

AN:

112239

Hom.:

Cov.:

AF XY:

0.000697

AC XY:

AN XY:

34439

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30876

American (AMR)

AF:

0.000188

AC:

AN:

10647

Ashkenazi Jewish (ASJ)

AF:

0.000378

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3543

South Asian (SAS)

AF:

0.0104

AC:

AN:

2701

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

6162

Middle Eastern (MID)

AF:

0.00463

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000394

AC:

AN:

53237

Other (OTH)

AF:

0.00

AC:

AN:

1524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.000212

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00211

AC:

256

EpiCase

AF:

0.000491

EpiControl

AF:

0.000712

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DIPK2B-related disorder

Benign:1

Oct 10, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-0.89

PhyloP100

0.87

PROVEAN

Benign

-1.5

N;D

REVEL

Benign

0.11

Sift

Benign

0.18

T;D

Sift4G

Benign

0.17

T;D

Vest4

0.16

MVP

0.65

MPC

0.73

ClinPred

0.077

GERP RS

4.3

gMVP

0.77

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

NM_176819.4:c.313T>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