chr6-24205008-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016356.5(DCDC2):c.1017C>T(p.Val339Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,612,470 control chromosomes in the GnomAD database, including 15,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1454 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14066 hom. )

Consequence

DCDC2
NM_016356.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.29

Publications

18 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-24205008-G-A is Benign according to our data. Variant chr6-24205008-G-A is described in ClinVar as Benign. ClinVar VariationId is 517825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5 link	c.1017C>T	p.Val339Val	synonymous_variant	Exon 8 of 10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.1017C>T	p.Val339Val	synonymous_variant	Exon 9 of 11		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8 link	c.1017C>T	p.Val339Val	synonymous_variant	Exon 8 of 10	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1
DCDC2	ENST00000378450.6 link	c.276C>T	p.Val92Val	synonymous_variant	Exon 1 of 3	1		ENSP00000367711.3		Q9UHG0-2

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20492

AN:

151952

Hom.:

1452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.0473

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0648

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.159

GnomAD2 exomes

AF:

0.125

AC:

31389

AN:

250326

AF XY:

0.129

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.0893

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0509

Gnomad FIN exome

AF:

0.0676

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.135

AC:

197766

AN:

1460400

Hom.:

14066

Cov.:

AF XY:

0.136

AC XY:

98972

AN XY:

726374

show subpopulations

African (AFR)

AF:

0.141

AC:

4712

AN:

33404

American (AMR)

AF:

0.0938

AC:

4187

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

4693

AN:

26084

East Asian (EAS)

AF:

0.0444

AC:

1762

AN:

39676

South Asian (SAS)

AF:

0.152

AC:

13080

AN:

86060

European-Finnish (FIN)

AF:

0.0703

AC:

3753

AN:

53384

Middle Eastern (MID)

AF:

0.178

AC:

1023

AN:

5758

European-Non Finnish (NFE)

AF:

0.140

AC:

156079

AN:

1111066

Other (OTH)

AF:

0.140

AC:

8477

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

8737

17473

26210

34946

43683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5448

10896

16344

21792

27240

<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:

0.135

AC:

20506

AN:

152070

Hom.:

1454

Cov.:

AF XY:

0.130

AC XY:

9677

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.139

AC:

5758

AN:

41494

American (AMR)

AF:

0.121

AC:

1846

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

593

AN:

3468

East Asian (EAS)

AF:

0.0472

AC:

244

AN:

5172

South Asian (SAS)

AF:

0.150

AC:

720

AN:

4816

European-Finnish (FIN)

AF:

0.0648

AC:

685

AN:

10572

Middle Eastern (MID)

AF:

0.182

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.147

AC:

9977

AN:

67974

Other (OTH)

AF:

0.159

AC:

336

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

911

1822

2732

3643

4554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.147

Hom.:

2104

Bravo

AF:

0.140

Asia WGS

AF:

0.0970

AC:

336

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.156

ClinVar

Significance: Benign

Submissions summary: Benign:5

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. -

Isolated neonatal sclerosing cholangitis

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Autosomal recessive nonsyndromic hearing loss 66

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephronophthisis 19

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

-0.81

CADD

Benign

0.064

(source)

DANN

Benign

0.82

PhyloP100

-2.3

PromoterAI

-0.0092

Neutral

(source)

Mutation Taster

=99/1

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