NM_016356.5:c.349-8372T>A

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

2

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

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
DCDC2NM_016356.5 linkc.349-8372T>A intron_variant Intron 2 of 9 ENST00000378454.8 NP_057440.2
DCDC2NM_001195610.2 linkc.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
DCDC2ENST00000378454.8 linkc.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.:
32
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.:
32
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
0
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
0
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
DANN
Benign
0.83
PhyloP100
-0.14
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs807685; hg19: chr6-24310644; API