X-111312405-C-T

Variant names:

• chrX-111312405-C-T
• rs41311727
• NM_001195553.2:c.1044+234G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001195553.2(DCX):​c.1044+234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 111,328 control chromosomes in the GnomAD database, including 500 homozygotes. There are 1,907 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.064 (500 hom., 1907 hem., cov: 23)
• Consequence: DCX NM_001195553.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-111312405-C-T is Benign according to our data. Variant chrX-111312405-C-T is described in ClinVar as [Benign]. Clinvar id is 676961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCX	NM_001195553.2	c.1044+234G>A		intron_variant	Intron 6 of 6	ENST00000636035.2	NP_001182482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCX	ENST00000636035.2	c.1044+234G>A		intron_variant	Intron 6 of 6	2	NM_001195553.2	ENSP00000490614.1
DCX	ENST00000356220.8	c.1044+234G>A		intron_variant	Intron 7 of 7	5		ENSP00000348553.4
DCX	ENST00000637453.1	c.1044+234G>A		intron_variant	Intron 6 of 6	5		ENSP00000490357.1
DCX	ENST00000637570.1	c.1029+234G>A		intron_variant	Intron 6 of 6	5		ENSP00000490878.1

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 7071 AN: 111275 Hom.: 499 Cov.: 23 AF XY: 0.0567 AC XY: 1900 AN XY: 33539

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.00681

Gnomad EAS AF: 0.000283

Gnomad SAS AF: 0.00188

Gnomad FIN AF: 0.000823

Gnomad MID AF: 0.0295

Gnomad NFE AF: 0.00569

Gnomad OTH AF: 0.0510

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0636 AC: 7079 AN: 111328 Hom.: 500 Cov.: 23 AF XY: 0.0568 AC XY: 1907 AN XY: 33602

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.0361

Gnomad4 ASJ AF: 0.00681

Gnomad4 EAS AF: 0.000284

Gnomad4 SAS AF: 0.00113

Gnomad4 FIN AF: 0.000823

Gnomad4 NFE AF: 0.00569

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.000688 Hom.: 3

Bravo AF: 0.0743

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.90
CADD	Benign	0.20
DANN	Benign	0.55

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: rs41311727; hg19: chrX-110555633;