chr6-24178448-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016356.5(DCDC2):c.1208G>A(p.Arg403His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,614,202 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

DCDC2
NM_016356.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0360

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=0.006783217).

BP6

Variant 6-24178448-C-T is Benign according to our data. Variant chr6-24178448-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 466322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00194 (296/152314) while in subpopulation AFR AF= 0.00679 (282/41558). AF 95% confidence interval is 0.00613. There are 2 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5 link	c.1208G>A	p.Arg403His	missense_variant	Exon 9 of 10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.1208G>A	p.Arg403His	missense_variant	Exon 10 of 11		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8 link	c.1208G>A	p.Arg403His	missense_variant	Exon 9 of 10	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1
DCDC2	ENST00000378450.6 link	c.467G>A	p.Arg156His	missense_variant	Exon 2 of 3	1		ENSP00000367711.3		Q9UHG0-2

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

295

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000489

AC:

123

AN:

251466

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00603

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000215

AC:

314

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

118

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00621

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.000430

GnomAD4 genome

AF:

0.00194

AC:

296

AN:

152314

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00679

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000346

Hom.:

Bravo

AF:

0.00222

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000618

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 10, 2017

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 66;C4479344:Isolated neonatal sclerosing cholangitis

Benign:1

May 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 02, 2018

GeneDx

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

0.077

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.0

DANN

Benign

0.93

DEOGEN2

Benign

0.039

.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.0068

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.41

.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.028

Sift

Benign

0.073

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.022

B;B

Vest4

0.24

MVP

0.58

MPC

0.14

ClinPred

0.018

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.20

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