NM_016356.5:c.294-13_294-10delGTTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_016356.5(DCDC2):c.294-13_294-10delGTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,561,562 control chromosomes in the GnomAD database, including 376 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 24 hom., cov: 32)

Exomes 𝑓: 0.018 ( 352 hom. )

Consequence

DCDC2
NM_016356.5 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.0670

Publications

0 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 -16 ACMG points.

BP6

Variant 6-24353632-AAAAC-A is Benign according to our data. Variant chr6-24353632-AAAAC-A is described in ClinVar as Benign. ClinVar VariationId is 466324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0158 (2402/152340) while in subpopulation NFE AF = 0.0216 (1468/68028). AF 95% confidence interval is 0.0207. There are 24 homozygotes in GnomAd4. There are 1219 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 24 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5 link	c.294-13_294-10delGTTT		intron_variant	Intron 1 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.294-13_294-10delGTTT		intron_variant	Intron 2 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8 link	c.294-13_294-10delGTTT		intron_variant	Intron 1 of 9	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1
DCDC2	ENST00000436313.1 link	c.195-13_195-10delGTTT		intron_variant	Intron 1 of 2	3		ENSP00000410939.1		H0Y784

Frequencies

GnomAD3 genomes

AF:

0.0158

AC:

2402

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00569

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0151

AC:

3457

AN:

229264

AF XY:

0.0153

show subpopulations

Gnomad AFR exome

AF:

0.00563

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.00376

Gnomad EAS exome

AF:

0.000711

Gnomad FIN exome

AF:

0.0345

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0181

AC:

25483

AN:

1409222

Hom.:

352

AF XY:

0.0177

AC XY:

12403

AN XY:

702366

show subpopulations

African (AFR)

AF:

0.00450

AC:

142

AN:

31552

American (AMR)

AF:

0.0106

AC:

402

AN:

37928

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

100

AN:

24794

East Asian (EAS)

AF:

0.000612

AC:

AN:

39242

South Asian (SAS)

AF:

0.00386

AC:

308

AN:

79808

European-Finnish (FIN)

AF:

0.0346

AC:

1759

AN:

50894

Middle Eastern (MID)

AF:

0.00161

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.0202

AC:

21787

AN:

1081006

Other (OTH)

AF:

0.0163

AC:

952

AN:

58424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

981

1961

2942

3922

4903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.0158

AC:

2402

AN:

152340

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1219

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00570

AC:

237

AN:

41588

American (AMR)

AF:

0.0156

AC:

239

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.000963

AC:

AN:

5190

South Asian (SAS)

AF:

0.00435

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0365

AC:

387

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0216

AC:

1468

AN:

68028

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

108

216

325

433

541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0177

Hom.:

Bravo

AF:

0.0130

Asia WGS

AF:

0.00348

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 31, 2018

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

Nov 19, 2018

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

PhyloP100

0.067

Mutation Taster

=100/0

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