Variant 20-45406596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000372720.7(DBNDD2):c.145C>T(p.Arg49Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

DBNDD2
ENST00000372720.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.729

Variant links:

Genes affected

DBNDD2 (HGNC:15881): (dysbindin domain containing 2) Involved in negative regulation of protein kinase activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DBNDD2 links:

SYS1-DBNDD2 (HGNC:):

SYS1-DBNDD2 links:

TP53TG5 (HGNC:15856): (TP53 target 5) Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

TP53TG5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18071255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYS1-DBNDD2	NR_003189.2 linkuse as main transcript	n.381-1864C>T		intron_variant, non_coding_transcript_variant
LOC107985404	XR_007067608.1 linkuse as main transcript	n.142-164G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
DBNDD2	ENST00000372720.7 linkuse as main transcript	c.145C>T	p.Arg49Trp	missense_variant	1/4	1		Q9BQY9-1
DBNDD2	ENST00000372717.5 linkuse as main transcript	c.-145C>T		5_prime_UTR_variant	1/4	5		Q9BQY9-3
DBNDD2	ENST00000357275.6 linkuse as main transcript	c.-9+341C>T		intron_variant		5	P1	Q9BQY9-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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

GnomAD4 exome

AF:

7.70e-7

AC:

AN:

1298512

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

633472

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.70e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

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

Bravo

AF:

0.00000378

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

May 18, 2023

The c.145C>T (p.R49W) alteration is located in exon 1 (coding exon 1) of the DBNDD2 gene. This alteration results from a C to T substitution at nucleotide position 145, causing the arginine (R) at amino acid position 49 to be replaced by a tryptophan (W). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Benign

0.064

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;D;D;D;N

PROVEAN

Benign

-1.2

REVEL

Benign

0.082

Sift

Uncertain

0.026

Sift4G

Uncertain

0.025

Vest4

0.23

MutPred

0.20

Loss of methylation at R49 (P = 0.0305);

MVP

0.78

ClinPred

0.34

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.26

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

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