chrX-111400961-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

lissencephaly spectrum disorders
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
lissencephaly type 1 due to doublecortin gene mutation
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
subcortical band heterotopia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DCX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 262925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
DCX	NM_001195553.2 link	c.705+29G>A		intron_variant	Intron 3 of 6	ENST00000636035.2	NP_001182482.1	A8K340

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DCX	ENST00000636035.2 link	c.705+29G>A	intron_variant	Intron 3 of 6	2	NM_001195553.2	ENSP00000490614.1	A8K340
DCX	ENST00000356220.8 link	c.705+29G>A	intron_variant	Intron 4 of 7	5		ENSP00000348553.4	A8K340
DCX	ENST00000637453.1 link	c.705+29G>A	intron_variant	Intron 3 of 6	5		ENSP00000490357.1	A8K340
DCX	ENST00000637570.1 link	c.705+29G>A	intron_variant	Intron 3 of 6	5		ENSP00000490878.1	A0A1B0GWD1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

1899

AN:

112089

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00713

AC:

1271

AN:

178369

AF XY:

0.00602

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 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

African (AFR)

AF:

0.0563

AC:

1450

AN:

25739

American (AMR)

AF:

0.00431

AC:

151

AN:

35062

Ashkenazi Jewish (ASJ)

AF:

0.000261

AC:

AN:

19144

East Asian (EAS)

AF:

0.000234

AC:

AN:

29963

South Asian (SAS)

AF:

0.00969

AC:

515

AN:

53149

European-Finnish (FIN)

AF:

0.000672

AC:

AN:

40150

Middle Eastern (MID)

AF:

0.00692

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

0.00303

AC:

2455

AN:

810698

Other (OTH)

AF:

0.00614

AC:

276

AN:

44979

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

176

352

529

705

881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0169

AC:

1899

AN:

112144

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

481

AN XY:

34358

show subpopulations

African (AFR)

AF:

0.0510

AC:

1574

AN:

30840

American (AMR)

AF:

0.00857

AC:

AN:

10622

Ashkenazi Jewish (ASJ)

AF:

0.000378

AC:

AN:

2649

East Asian (EAS)

AF:

0.000280

AC:

AN:

3573

South Asian (SAS)

AF:

0.0116

AC:

AN:

2680

European-Finnish (FIN)

AF:

0.000491

AC:

AN:

6115

Middle Eastern (MID)

AF:

0.0138

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00340

AC:

181

AN:

53237

Other (OTH)

AF:

0.00917

AC:

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

149

223

298

372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.74

PhyloP100

0.025

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over