Variant 20-45410032-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001048225.4(DBNDD2):c.378C>A(p.Asn126Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,552,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DBNDD2
NM_001048225.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.238

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 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=0.15654641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBNDD2	NM_001048225.4 linkuse as main transcript	c.378C>A	p.Asn126Lys	missense_variant	3/3	ENST00000372710.5
SYS1-DBNDD2	NR_003189.2 linkuse as main transcript	n.766C>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.378C>A	p.Asn126Lys	missense_variant	3/3	1	NM_001048225.4	P1	Q9BQY9-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1400688

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690906

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:

9.26e-7

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000611

Hom.:

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

Aug 03, 2022

The c.684C>A (p.N228K) 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 684, causing the asparagine (N) at amino acid position 228 to be replaced by a lysine (K). 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

0.35

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Benign

0.85

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.69

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Benign

0.069

Sift

Benign

0.55

T;T;T;T;T;T

Sift4G

Benign

0.69

T;T;T;T;T;T

Polyphen

0.085

.;.;B;.;.;.

Vest4

0.16

MutPred

0.52

.;.;Gain of ubiquitination at N224 (P = 0.0066);.;.;.;

MVP

0.42

MPC

0.37

ClinPred

0.32

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.044

gMVP

0.15

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