Variant rs61036541 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001195553.2(DCX):c.705+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,175,072 control chromosomes in the GnomAD database, including 70 homozygotes. There are 2,072 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 35 hom., 481 hem., cov: 23)

Exomes 𝑓: 0.0046 ( 35 hom. 1591 hem. )

Consequence

DCX
NM_001195553.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0250

Variant links:

Genes affected

DCX (HGNC:2714): (doublecortin) This gene encodes a member of the doublecortin family. The protein encoded by this gene is a cytoplasmic protein and contains two doublecortin domains, which bind microtubules. In the developing cortex, cortical neurons must migrate over long distances to reach the site of their final differentiation. The encoded protein appears to direct neuronal migration by regulating the organization and stability of microtubules. In addition, the encoded protein interacts with LIS1, the regulatory gamma subunit of platelet activating factor acetylhydrolase, and this interaction is important to proper microtubule function in the developing cortex. Mutations in this gene cause abnormal migration of neurons during development and disrupt the layering of the cortex, leading to epilepsy, cognitive disability, subcortical band heterotopia ("double cortex" syndrome) in females and lissencephaly ("smooth brain" syndrome) in males. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

DCX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-111400961-C-T is Benign according to our data. Variant chrX-111400961-C-T is described in ClinVar as [Benign]. Clinvar id is 262925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111400961-C-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCX	NM_001195553.2 linkuse as main transcript	c.705+29G>A		intron_variant		ENST00000636035.2	NP_001182482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCX	ENST00000636035.2 linkuse as main transcript	c.705+29G>A		intron_variant		2	NM_001195553.2	ENSP00000490614	A1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

1899

AN:

112089

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

478

AN XY:

34293

show subpopulations

Gnomad AFR

AF:

0.0512

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00858

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.0115

Gnomad FIN

AF:

0.000491

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.00929

GnomAD3 exomes

AF:

0.00713

AC:

1271

AN:

178369

Hom.:

AF XY:

0.00602

AC XY:

391

AN XY:

64973

show subpopulations

Gnomad AFR exome

AF:

0.0572

Gnomad AMR exome

AF:

0.00361

Gnomad ASJ exome

AF:

0.000136

Gnomad EAS exome

AF:

0.0000731

Gnomad SAS exome

AF:

0.00828

Gnomad FIN exome

AF:

0.000391

Gnomad NFE exome

AF:

0.00321

Gnomad OTH exome

AF:

0.00519

GnomAD4 exome

AF:

0.00462

AC:

4914

AN:

1062928

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

1591

AN XY:

333760

show subpopulations

Gnomad4 AFR exome

AF:

0.0563

Gnomad4 AMR exome

AF:

0.00431

Gnomad4 ASJ exome

AF:

0.000261

Gnomad4 EAS exome

AF:

0.000234

Gnomad4 SAS exome

AF:

0.00969

Gnomad4 FIN exome

AF:

0.000672

Gnomad4 NFE exome

AF:

0.00303

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.0169

AC:

1899

AN:

112144

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

481

AN XY:

34358

show subpopulations

Gnomad4 AFR

AF:

0.0510

Gnomad4 AMR

AF:

0.00857

Gnomad4 ASJ

AF:

0.000378

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.000491

Gnomad4 NFE

AF:

0.00340

Gnomad4 OTH

AF:

0.00917

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0191

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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