chr6-24174793-T-A

Position:

chr6-24174793-T-A

Variant summary

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

The NM_016356.5(DCDC2):c.1368A>T(p.Lys456Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 1,613,154 control chromosomes in the GnomAD database, including 8,576 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 4079 hom., cov: 32)

Exomes 𝑓: 0.039 ( 4497 hom. )

Consequence

DCDC2
NM_016356.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

DCDC2 (HGNC:18141): (doublecortin domain containing 2) This gene encodes a doublecortin domain-containing family member. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. This family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. Mutations in this gene have been associated with reading disability (RD) type 2, also referred to as developmental dyslexia. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2013]

DCDC2 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=0.0032149553).

BP6

Variant 6-24174793-T-A is Benign according to our data. Variant chr6-24174793-T-A is described in ClinVar as [Benign]. Clinvar id is 508595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5 linkuse as main transcript	c.1368A>T	p.Lys456Asn	missense_variant	10/10	ENST00000378454.8
DCDC2	NM_001195610.2 linkuse as main transcript	c.1368A>T	p.Lys456Asn	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8 linkuse as main transcript	c.1368A>T	p.Lys456Asn	missense_variant	10/10	1	NM_016356.5	P1	Q9UHG0-1
DCDC2	ENST00000378450.6 linkuse as main transcript	c.627A>T	p.Lys209Asn	missense_variant	3/3	1			Q9UHG0-2

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21702

AN:

152000

Hom.:

4078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.438

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0832

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.0500

AC:

12552

AN:

251094

Hom.:

1666

AF XY:

0.0404

AC XY:

5481

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.445

Gnomad AMR exome

AF:

0.0477

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.00337

Gnomad NFE exome

AF:

0.0271

Gnomad OTH exome

AF:

0.0382

GnomAD4 exome

AF:

0.0389

AC:

56887

AN:

1461036

Hom.:

4497

Cov.:

AF XY:

0.0363

AC XY:

26369

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.459

Gnomad4 AMR exome

AF:

0.0514

Gnomad4 ASJ exome

AF:

0.0275

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00246

Gnomad4 FIN exome

AF:

0.00399

Gnomad4 NFE exome

AF:

0.0313

Gnomad4 OTH exome

AF:

0.0513

GnomAD4 genome

AF:

0.143

AC:

21731

AN:

152118

Hom.:

4079

Cov.:

AF XY:

0.137

AC XY:

10208

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.437

Gnomad4 AMR

AF:

0.0830

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.0427

Hom.:

471

Bravo

AF:

0.163

TwinsUK

AF:

0.0343

AC:

127

ALSPAC

AF:

0.0371

AC:

143

ESP6500AA

AF:

0.418

AC:

1840

ESP6500EA

AF:

0.0286

AC:

246

ExAC

AF:

0.0559

AC:

6790

Asia WGS

AF:

0.0280

AC:

AN:

3476

EpiCase

AF:

0.0254

EpiControl

AF:

0.0257

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive nonsyndromic hearing loss 66;C4479344:Isolated neonatal sclerosing cholangitis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

.;T

Eigen

Benign

0.049

Eigen_PC

Benign

0.098

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.087

Sift

Benign

0.030

D;T

Sift4G

Benign

0.15

T;T

Polyphen

0.93

P;P

Vest4

0.067

MutPred

0.094

.;Loss of ubiquitination at K456 (P = 0.0022);

MPC

0.25

ClinPred

0.016

GERP RS

3.3

Varity_R

0.084

gMVP

0.17

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