NM_016356.5:c.183C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_016356.5(DCDC2):c.183C>T(p.Ala61Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,613,326 control chromosomes in the GnomAD database, including 2,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 198 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2410 hom. )

Consequence

DCDC2
NM_016356.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.41

Publications

7 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 links:

KAAG1 (HGNC:21031): (kidney associated DCDC2 antisense RNA 1)

KAAG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.12).

BP6

Variant 6-24357568-G-A is Benign according to our data. Variant chr6-24357568-G-A is described in ClinVar as Benign. ClinVar VariationId is 466323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DCDC2	NM_016356.5 link	c.183C>T	p.Ala61Ala	synonymous_variant	Exon 1 of 10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.183C>T	p.Ala61Ala	synonymous_variant	Exon 2 of 11		NP_001182539.1
KAAG1	NR_174942.1 link	n.666G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DCDC2	ENST00000378454.8 link	c.183C>T	p.Ala61Ala	synonymous_variant	Exon 1 of 10	1	NM_016356.5	ENSP00000367715.3	Q9UHG0-1
KAAG1	ENST00000274766.2 link	n.666G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6	NM_181337.4
DCDC2	ENST00000436313.1 link	c.84C>T	p.Ala28Ala	synonymous_variant	Exon 1 of 3	3		ENSP00000410939.1	H0Y784

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6625

AN:

152030

Hom.:

197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.0514

Gnomad ASJ

AF:

0.0697

Gnomad EAS

AF:

0.00503

Gnomad SAS

AF:

0.0523

Gnomad FIN

AF:

0.0269

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0635

Gnomad OTH

AF:

0.0523

GnomAD2 exomes

AF:

0.0471

AC:

11665

AN:

247886

AF XY:

0.0489

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.0330

Gnomad ASJ exome

AF:

0.0712

Gnomad EAS exome

AF:

0.00223

Gnomad FIN exome

AF:

0.0336

Gnomad NFE exome

AF:

0.0622

Gnomad OTH exome

AF:

0.0540

GnomAD4 exome

AF:

0.0547

AC:

79963

AN:

1461178

Hom.:

2410

Cov.:

AF XY:

0.0549

AC XY:

39873

AN XY:

726898

show subpopulations

African (AFR)

AF:

0.0120

AC:

402

AN:

33480

American (AMR)

AF:

0.0346

AC:

1547

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

1845

AN:

26136

East Asian (EAS)

AF:

0.00212

AC:

AN:

39700

South Asian (SAS)

AF:

0.0522

AC:

4500

AN:

86254

European-Finnish (FIN)

AF:

0.0350

AC:

1844

AN:

52726

Middle Eastern (MID)

AF:

0.0690

AC:

398

AN:

5768

European-Non Finnish (NFE)

AF:

0.0593

AC:

65951

AN:

1112000

Other (OTH)

AF:

0.0562

AC:

3392

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

5077

10153

15230

20306

25383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2300

4600

6900

9200

11500

<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:

0.0436

AC:

6628

AN:

152148

Hom.:

198

Cov.:

AF XY:

0.0417

AC XY:

3104

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0123

AC:

509

AN:

41522

American (AMR)

AF:

0.0514

AC:

786

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0697

AC:

242

AN:

3472

East Asian (EAS)

AF:

0.00504

AC:

AN:

5158

South Asian (SAS)

AF:

0.0530

AC:

255

AN:

4814

European-Finnish (FIN)

AF:

0.0269

AC:

286

AN:

10614

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0635

AC:

4317

AN:

67974

Other (OTH)

AF:

0.0522

AC:

110

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

329

658

986

1315

1644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0438

Hom.:

160

Bravo

AF:

0.0428

Asia WGS

AF:

0.0340

AC:

117

AN:

3478

EpiCase

AF:

0.0692

EpiControl

AF:

0.0686

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 09, 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

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.3

(source)

DANN

Benign

0.92

PhyloP100

-3.4

PromoterAI

0.0096

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=281/19

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

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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