rs61036541

chrX-111400961-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0250

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]

ACMG classification

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	UniProt
DCX	NM_001195553.2	c.705+29G>A		intron_variant		ENST00000636035.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 1899 AN: 112089 Hom.: 35 Cov.: 23 AF XY: 0.0139 AC XY: 478 AN XY: 34293

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.: 20 AF XY: 0.00602 AC XY: 391 AN XY: 64973

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.: 35 Cov.: 26 AF XY: 0.00477 AC XY: 1591 AN XY: 333760

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.: 35 Cov.: 23 AF XY: 0.0140 AC XY: 481 AN XY: 34358

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.: 70

Bravo AF: 0.0191

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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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

Other links and lift over

dbSNP: rs61036541; hg19: chrX-110644189;