6-24301818-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016356.5(DCDC2):c.454C>G(p.Pro152Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0391 in 1,614,066 control chromosomes in the GnomAD database, including 1,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P152P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.039 ( 124 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1227 hom. )

Consequence

DCDC2
NM_016356.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.59

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
isolated neonatal sclerosing cholangitis
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
nephronophthisis 19
Inheritance: AR Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Boichis syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 66
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

DCDC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004606217).

BP6

Variant 6-24301818-G-C is Benign according to our data. Variant chr6-24301818-G-C is described in CliVar as Benign. Clinvar id is 466326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24301818-G-C is described in CliVar as Benign. Clinvar id is 466326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24301818-G-C is described in CliVar as Benign. Clinvar id is 466326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24301818-G-C is described in CliVar as Benign. Clinvar id is 466326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5 link	c.454C>G	p.Pro152Ala	missense_variant	Exon 4 of 10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.454C>G	p.Pro152Ala	missense_variant	Exon 5 of 11		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8 link	c.454C>G	p.Pro152Ala	missense_variant	Exon 4 of 10	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5971

AN:

152108

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.0350

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.0150

Gnomad SAS

AF:

0.0626

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0387

GnomAD2 exomes

AF:

0.0373

AC:

9377

AN:

251470

AF XY:

0.0384

show subpopulations

Gnomad AFR exome

AF:

0.0414

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.0570

Gnomad EAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.0174

Gnomad NFE exome

AF:

0.0419

Gnomad OTH exome

AF:

0.0456

GnomAD4 exome

AF:

0.0391

AC:

57199

AN:

1461840

Hom.:

1227

Cov.:

AF XY:

0.0397

AC XY:

28857

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0424

AC:

1420

AN:

33480

American (AMR)

AF:

0.0256

AC:

1144

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

1536

AN:

26134

East Asian (EAS)

AF:

0.0168

AC:

668

AN:

39696

South Asian (SAS)

AF:

0.0527

AC:

4550

AN:

86258

European-Finnish (FIN)

AF:

0.0177

AC:

946

AN:

53420

Middle Eastern (MID)

AF:

0.0534

AC:

308

AN:

5768

European-Non Finnish (NFE)

AF:

0.0396

AC:

44041

AN:

1111966

Other (OTH)

AF:

0.0428

AC:

2586

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

2951

5903

8854

11806

14757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1586

3172

4758

6344

7930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0393

AC:

5979

AN:

152226

Hom.:

124

Cov.:

AF XY:

0.0374

AC XY:

2786

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0405

AC:

1680

AN:

41522

American (AMR)

AF:

0.0350

AC:

535

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

180

AN:

3468

East Asian (EAS)

AF:

0.0148

AC:

AN:

5186

South Asian (SAS)

AF:

0.0631

AC:

304

AN:

4818

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10612

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0424

AC:

2880

AN:

68004

Other (OTH)

AF:

0.0388

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

296

592

887

1183

1479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0428

Hom.:

Bravo

AF:

0.0413

TwinsUK

AF:

0.0334

AC:

124

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.0361

AC:

159

ESP6500EA

AF:

0.0420

AC:

361

ExAC

AF:

0.0383

AC:

4652

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

EpiCase

AF:

0.0473

EpiControl

AF:

0.0465

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 16, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 26, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0046

MetaSVM

Uncertain

0.61

MutationAssessor

Uncertain

2.5

PhyloP100

4.6

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-6.4

REVEL

Uncertain

0.44

Sift

Benign

0.037

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.18

MPC

0.44

ClinPred

0.019

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.41

Mutation Taster

=29/71

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over