Variant X-45191837-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_176819.4(DIPK2B):c.412A>T(p.Thr138Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,210,468 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 8 hem., cov: 24)

Exomes 𝑓: 0.000013 ( 0 hom. 1 hem. )

Consequence

DIPK2B
NM_176819.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

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:

DIPK2B (HGNC:):

DIPK2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03919944).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK2B	NM_176819.4 linkuse as main transcript	c.412A>T	p.Thr138Ser	missense_variant	2/5	ENST00000398000.7	NP_789789.2	Q9H7Y0-1Q8WZ11
DIPK2B	NM_024689.3 linkuse as main transcript	c.412A>T	p.Thr138Ser	missense_variant	2/3		NP_078965.2	Q9H7Y0-2
DIPK2B	XM_005272670.1 linkuse as main transcript	c.412A>T	p.Thr138Ser	missense_variant	2/4		XP_005272727.1
DIPK2B	XM_006724559.1 linkuse as main transcript	c.412A>T	p.Thr138Ser	missense_variant	2/4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7 linkuse as main transcript	c.412A>T	p.Thr138Ser	missense_variant	2/5	5	NM_176819.4	ENSP00000381086.2		Q9H7Y0-1

Frequencies

GnomAD3 genomes

AF:

0.000133

AC:

AN:

112363

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

34541

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

183319

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67767

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000328

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000127

AC:

AN:

1098105

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363459

show subpopulations

Gnomad4 AFR exome

AF:

0.0000757

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000133

AC:

AN:

112363

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

34541

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000159

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.412A>T (p.T138S) alteration is located in exon 2 (coding exon 2) of the CXorf36 gene. This alteration results from a A to T substitution at nucleotide position 412, causing the threonine (T) at amino acid position 138 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Benign

0.83

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.99

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.14

Sift

Benign

0.88

T;T

Sift4G

Benign

0.73

T;T

Vest4

0.051

MutPred

0.19

Gain of disorder (P = 0.0236);Gain of disorder (P = 0.0236);

MVP

0.67

MPC

0.21

ClinPred

0.026

GERP RS

4.5

gMVP

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over