Variant 12-48996894-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015086.2(DDN):c.1982A>G(p.Glu661Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,613,036 control chromosomes in the GnomAD database, including 126,965 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.42 ( 13821 hom., cov: 33)

Exomes 𝑓: 0.39 ( 113144 hom. )

Consequence

DDN
NM_015086.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.769

Variant links:

Genes affected

DDN (HGNC:24458): (dendrin) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cell projection and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DDN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3861852E-5).

BP6

Variant 12-48996894-T-C is Benign according to our data. Variant chr12-48996894-T-C is described in ClinVar as [Benign]. Clinvar id is 1244708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDN	NM_015086.2 linkuse as main transcript	c.1982A>G	p.Glu661Gly	missense_variant	2/2	ENST00000421952.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDN	ENST00000421952.3 linkuse as main transcript	c.1982A>G	p.Glu661Gly	missense_variant	2/2	1	NM_015086.2	P1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63804

AN:

151988

Hom.:

13788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.380

GnomAD3 exomes

AF:

0.384

AC:

95542

AN:

248894

Hom.:

18908

AF XY:

0.386

AC XY:

52030

AN XY:

134692

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.438

Gnomad SAS exome

AF:

0.434

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.390

AC:

570105

AN:

1460928

Hom.:

113144

Cov.:

AF XY:

0.390

AC XY:

283779

AN XY:

726766

show subpopulations

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.429

Gnomad4 FIN exome

AF:

0.413

Gnomad4 NFE exome

AF:

0.390

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.420

AC:

63896

AN:

152108

Hom.:

13821

Cov.:

AF XY:

0.418

AC XY:

31103

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.426

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.413

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.379

Alfa

AF:

0.382

Hom.:

28925

Bravo

AF:

0.412

TwinsUK

AF:

0.379

AC:

1407

ALSPAC

AF:

0.400

AC:

1543

ESP6500AA

AF:

0.512

AC:

2254

ESP6500EA

AF:

0.373

AC:

3211

ExAC

AF:

0.387

AC:

47019

Asia WGS

AF:

0.438

AC:

1521

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 26, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.3

DANN

Benign

0.69

DEOGEN2

Benign

0.011

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.12

MetaRNN

Benign

0.000024

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

2.3

REVEL

Benign

0.029

Sift

Benign

0.75

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.0080

MPC

0.74

ClinPred

0.00095

GERP RS

-5.8

Varity_R

0.025

gMVP

0.019

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