dbSNP rs10498720: DCDC2:c.348+361T>G (chr6-24353208-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016356.5(DCDC2):c.348+361T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 449,126 control chromosomes in the GnomAD database, including 1,684 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.045 ( 355 hom., cov: 33)

Exomes 𝑓: 0.070 ( 1329 hom. )

Consequence

DCDC2
NM_016356.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.111

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5 link	c.348+361T>G		intron_variant	Intron 2 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.348+361T>G		intron_variant	Intron 3 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8 link	c.348+361T>G		intron_variant	Intron 2 of 9	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1
DCDC2	ENST00000436313.1 link	c.*97T>G		downstream_gene_variant		3		ENSP00000410939.1		H0Y784

Frequencies

GnomAD3 genomes

AF:

0.0451

AC:

6860

AN:

152186

Hom.:

350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0339

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0329

Gnomad OTH

AF:

0.0492

GnomAD4 exome

AF:

0.0700

AC:

20778

AN:

296822

Hom.:

1329

Cov.:

AF XY:

0.0773

AC XY:

12983

AN XY:

167896

show subpopulations

African (AFR)

AF:

0.0119

AC:

AN:

7718

American (AMR)

AF:

0.124

AC:

2864

AN:

23132

Ashkenazi Jewish (ASJ)

AF:

0.0557

AC:

511

AN:

9182

East Asian (EAS)

AF:

0.206

AC:

1867

AN:

9084

South Asian (SAS)

AF:

0.160

AC:

8708

AN:

54366

European-Finnish (FIN)

AF:

0.0330

AC:

857

AN:

25960

Middle Eastern (MID)

AF:

0.0941

AC:

250

AN:

2656

European-Non Finnish (NFE)

AF:

0.0315

AC:

4769

AN:

151266

Other (OTH)

AF:

0.0639

AC:

860

AN:

13458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

878

1755

2633

3510

4388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<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:

0.0451

AC:

6869

AN:

152304

Hom.:

355

Cov.:

AF XY:

0.0496

AC XY:

3690

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0106

AC:

439

AN:

41580

American (AMR)

AF:

0.110

AC:

1686

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

184

AN:

3470

East Asian (EAS)

AF:

0.201

AC:

1041

AN:

5188

South Asian (SAS)

AF:

0.161

AC:

777

AN:

4824

European-Finnish (FIN)

AF:

0.0339

AC:

360

AN:

10610

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0329

AC:

2235

AN:

68028

Other (OTH)

AF:

0.0567

AC:

120

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

313

627

940

1254

1567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0393

Hom.:

395

Bravo

AF:

0.0455

Asia WGS

AF:

0.187

AC:

650

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.5

(source)

DANN

Benign

0.60

PhyloP100

0.11

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

Computational scores

Splicing

Publications

Other links and lift over