Variant 6-24174896-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016356.5(DCDC2):c.1327-62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 998,074 control chromosomes in the GnomAD database, including 24,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3584 hom., cov: 32)

Exomes 𝑓: 0.20 ( 20655 hom. )

Consequence

DCDC2
NM_016356.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.655

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 6-24174896-T-C is Benign according to our data. Variant chr6-24174896-T-C is described in ClinVar as [Benign]. Clinvar id is 682615.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5 link	c.1327-62A>G		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 link	c.1327-62A>G		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8 link	c.1327-62A>G		intron_variant		1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1
DCDC2	ENST00000378450.6 link	c.586-62A>G		intron_variant		1		ENSP00000367711.3		Q9UHG0-2

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30487

AN:

151882

Hom.:

3581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.176

GnomAD4 exome

AF:

0.199

AC:

168717

AN:

846076

Hom.:

20655

AF XY:

0.201

AC XY:

87306

AN XY:

434310

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.306

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.562

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.201

AC:

30518

AN:

151998

Hom.:

3584

Cov.:

AF XY:

0.205

AC XY:

15249

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.591

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.187

Hom.:

679

Bravo

AF:

0.207

Asia WGS

AF:

0.406

AC:

1409

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.4

DANN

Benign

0.87

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