Genetic Variant NM_016356.5:c.349-8372T>A (chr6-24310416-A-T) – 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.349-8372T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,076 control chromosomes in the GnomAD database, including 47,678 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 0.77 ( 47678 hom., cov: 32)

Consequence

DCDC2
NM_016356.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.145

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5 link	c.349-8372T>A		intron_variant	Intron 2 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.349-8372T>A		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.349-8372T>A		intron_variant	Intron 2 of 9	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

116995

AN:

151958

Hom.:

47671

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.834

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.915

Gnomad FIN

AF:

0.944

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.873

Gnomad OTH

AF:

0.798

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.770

AC:

117041

AN:

152076

Hom.:

47678

Cov.:

AF XY:

0.777

AC XY:

57779

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.471

AC:

19500

AN:

41410

American (AMR)

AF:

0.834

AC:

12753

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.887

AC:

3080

AN:

3472

East Asian (EAS)

AF:

0.995

AC:

5146

AN:

5172

South Asian (SAS)

AF:

0.914

AC:

4409

AN:

4822

European-Finnish (FIN)

AF:

0.944

AC:

10009

AN:

10602

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.873

AC:

59397

AN:

68000

Other (OTH)

AF:

0.799

AC:

1685

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1128

2257

3385

4514

5642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.805

Hom.:

6343

Bravo

AF:

0.745

Asia WGS

AF:

0.926

AC:

3218

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.2

(source)

DANN

Benign

0.83

PhyloP100

-0.14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over