rs141519329

Positions:

chr6-24278116-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016356.5(DCDC2):c.855A>G(p.Ser285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000646 in 1,614,010 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 3 hom. )

Consequence

DCDC2
NM_016356.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.109

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-24278116-T-C is Benign according to our data. Variant chr6-24278116-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 466327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24278116-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.109 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00232 (354/152382) while in subpopulation AFR AF= 0.00651 (271/41598). AF 95% confidence interval is 0.00588. There are 1 homozygotes in gnomad4. There are 192 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5 linkuse as main transcript	c.855A>G	p.Ser285=	synonymous_variant	7/10	ENST00000378454.8
DCDC2	NM_001195610.2 linkuse as main transcript	c.855A>G	p.Ser285=	synonymous_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8 linkuse as main transcript	c.855A>G	p.Ser285=	synonymous_variant	7/10	1	NM_016356.5	P1	Q9UHG0-1

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

353

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00405

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000928

AC:

233

AN:

251104

Hom.:

AF XY:

0.000671

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00763

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000471

AC:

689

AN:

1461628

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

286

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00723

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000271

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.00232

AC:

354

AN:

152382

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00651

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000976

Hom.:

Bravo

AF:

0.00274

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 26, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 19, 2017

- -

DCDC2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Autosomal recessive nonsyndromic hearing loss 66;C4015542:Nephronophthisis 19;C4479344:Isolated neonatal sclerosing cholangitis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.4

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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