6-24301818-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016356.5(DCDC2):c.454C>G(p.Pro152Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0391 in 1,614,066 control chromosomes in the GnomAD database, including 1,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 124 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1227 hom. )

Consequence

DCDC2
NM_016356.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.59

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004606217).

BP6

Variant 6-24301818-G-C is Benign according to our data. Variant chr6-24301818-G-C is described in ClinVar as [Benign]. Clinvar id is 466326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5 link	c.454C>G	p.Pro152Ala	missense_variant	Exon 4 of 10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.454C>G	p.Pro152Ala	missense_variant	Exon 5 of 11		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8 link	c.454C>G	p.Pro152Ala	missense_variant	Exon 4 of 10	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5971

AN:

152108

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.0350

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.0150

Gnomad SAS

AF:

0.0626

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0387

GnomAD3 exomes

AF:

0.0373

AC:

9377

AN:

251470

Hom.:

247

AF XY:

0.0384

AC XY:

5215

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0414

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.0570

Gnomad EAS exome

AF:

0.0114

Gnomad SAS exome

AF:

0.0539

Gnomad FIN exome

AF:

0.0174

Gnomad NFE exome

AF:

0.0419

Gnomad OTH exome

AF:

0.0456

GnomAD4 exome

AF:

0.0391

AC:

57199

AN:

1461840

Hom.:

1227

Cov.:

AF XY:

0.0397

AC XY:

28857

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0424

Gnomad4 AMR exome

AF:

0.0256

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.0168

Gnomad4 SAS exome

AF:

0.0527

Gnomad4 FIN exome

AF:

0.0177

Gnomad4 NFE exome

AF:

0.0396

Gnomad4 OTH exome

AF:

0.0428

GnomAD4 genome

AF:

0.0393

AC:

5979

AN:

152226

Hom.:

124

Cov.:

AF XY:

0.0374

AC XY:

2786

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0405

Gnomad4 AMR

AF:

0.0350

Gnomad4 ASJ

AF:

0.0519

Gnomad4 EAS

AF:

0.0148

Gnomad4 SAS

AF:

0.0631

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.0424

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0428

Hom.:

Bravo

AF:

0.0413

TwinsUK

AF:

0.0334

AC:

124

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.0361

AC:

159

ESP6500EA

AF:

0.0420

AC:

361

ExAC

AF:

0.0383

AC:

4652

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

EpiCase

AF:

0.0473

EpiControl

AF:

0.0465

ClinVar

Significance: Benign

Submissions summary: Benign:3

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. -

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

Feb 26, 2019

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0046

MetaSVM

Uncertain

0.61

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-6.4

REVEL

Uncertain

0.44

Sift

Benign

0.037

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.18

MPC

0.44

ClinPred

0.019

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over