rs143313706

Positions:

Variant summary

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

The NM_016356.5(DCDC2):c.1044C>T(p.Asp348Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,612,918 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 29 hom. )

Consequence

DCDC2
NM_016356.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.237

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=-0.49).

BP6

Variant 6-24178612-G-A is Benign according to our data. Variant chr6-24178612-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 466321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24178612-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.237 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0029 (441/152016) while in subpopulation AMR AF= 0.00399 (61/15270). AF 95% confidence interval is 0.00319. There are 4 homozygotes in gnomad4. There are 220 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5 linkuse as main transcript	c.1044C>T	p.Asp348Asp	synonymous_variant	9/10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 linkuse as main transcript	c.1044C>T	p.Asp348Asp	synonymous_variant	10/11		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8 linkuse as main transcript	c.1044C>T	p.Asp348Asp	synonymous_variant	9/10	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1
DCDC2	ENST00000378450.6 linkuse as main transcript	c.303C>T	p.Asp101Asp	synonymous_variant	2/3	1		ENSP00000367711.3		Q9UHG0-2

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

441

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00391

AC:

980

AN:

250470

Hom.:

AF XY:

0.00414

AC XY:

560

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.00400

Gnomad FIN exome

AF:

0.000377

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00315

AC:

4603

AN:

1460902

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

2390

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.0285

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.00407

Gnomad4 FIN exome

AF:

0.000170

Gnomad4 NFE exome

AF:

0.00273

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.00290

AC:

441

AN:

152016

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

220

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.000724

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.0303

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.00316

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00514

Hom.:

Bravo

AF:

0.00319

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00534

EpiControl

AF:

0.00557

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	DCDC2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 24, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 01, 2017	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 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

Nov 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.9

DANN

Benign

0.39

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