Variant X-111301414-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001195553.2(DCX):c.*273C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 402,534 control chromosomes in the GnomAD database, including 2 homozygotes. There are 181 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., 142 hem., cov: 23)

Exomes 𝑓: 0.00071 ( 0 hom. 39 hem. )

Consequence

DCX
NM_001195553.2 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.237

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant X-111301414-G-A is Benign according to our data. Variant chrX-111301414-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1212152.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00475 (531/111900) while in subpopulation AFR AF= 0.0161 (497/30799). AF 95% confidence interval is 0.015. There are 2 homozygotes in gnomad4. There are 142 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCX	NM_001195553.2 linkuse as main transcript	c.*273C>T		3_prime_UTR_variant	7/7	ENST00000636035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCX	ENST00000636035.2 linkuse as main transcript	c.*273C>T		3_prime_UTR_variant	7/7	2	NM_001195553.2	A1

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

528

AN:

111845

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

139

AN XY:

34011

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00237

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00465

GnomAD4 exome

AF:

0.000709

AC:

206

AN:

290634

Hom.:

Cov.:

AF XY:

0.000434

AC XY:

AN XY:

89760

show subpopulations

Gnomad4 AFR exome

AF:

0.0175

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000455

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00475

AC:

531

AN:

111900

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

142

AN XY:

34076

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.00237

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00459

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00621

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

DANN

Benign

0.52

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