Variant 20-45409998-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001048225.4(DBNDD2):c.344C>A(p.Thr115Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,502,796 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

DBNDD2
NM_001048225.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010281712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBNDD2	NM_001048225.4 linkuse as main transcript	c.344C>A	p.Thr115Asn	missense_variant	3/3	ENST00000372710.5
SYS1-DBNDD2	NR_003189.2 linkuse as main transcript	n.732C>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBNDD2	ENST00000372710.5 linkuse as main transcript	c.344C>A	p.Thr115Asn	missense_variant	3/3	1	NM_001048225.4	P1	Q9BQY9-2

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000382

AC:

AN:

146766

Hom.:

AF XY:

0.000411

AC XY:

AN XY:

77818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000362

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.000955

GnomAD4 exome

AF:

0.000177

AC:

239

AN:

1350996

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

134

AN XY:

665910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000328

Gnomad4 AMR exome

AF:

0.0000292

Gnomad4 ASJ exome

AF:

0.00392

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000784

Gnomad4 OTH exome

AF:

0.000451

GnomAD4 genome

AF:

0.000132

AC:

AN:

151800

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.000231

AC:

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

Mar 02, 2023

The c.650C>A (p.T217N) alteration is located in exon 3 (coding exon 3) of the DBNDD2 gene. This alteration results from a C to A substitution at nucleotide position 650, causing the threonine (T) at amino acid position 217 to be replaced by an asparagine (N). 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

0.16

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

0.13

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.86

M_CAP

Benign

0.014

MetaRNN

Benign

0.010

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;N;N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.1

N;N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.11

T;T;T;T;T;T

Sift4G

Benign

0.47

T;T;T;T;T;T

Polyphen

0.57

.;.;P;.;.;.

Vest4

0.13

MVP

0.46

MPC

0.69

ClinPred

0.070

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.055

gMVP

0.22

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