rs201805884
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001195553.2(DCX):c.705+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,105,353 control chromosomes in the GnomAD database, including 94 homozygotes. There are 4,095 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 0.0089 ( 16 hom., 295 hem., cov: 23)
Exomes 𝑓: 0.011 ( 78 hom. 3800 hem. )
Consequence
DCX
NM_001195553.2 intron
NM_001195553.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.840
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]
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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=-0.87).
BP6
Variant X-111400942-T-C is Benign according to our data. Variant chrX-111400942-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 262926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111400942-T-C is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00891 (1001/112359) while in subpopulation SAS AF= 0.0288 (77/2670). AF 95% confidence interval is 0.0237. There are 16 homozygotes in gnomad4. There are 295 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 16 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DCX | NM_001195553.2 | c.705+48A>G | intron_variant | ENST00000636035.2 | NP_001182482.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DCX | ENST00000636035.2 | c.705+48A>G | intron_variant | 2 | NM_001195553.2 | ENSP00000490614 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00893 AC: 1003AN: 112307Hom.: 16 Cov.: 23 AF XY: 0.00859 AC XY: 296AN XY: 34465
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GnomAD3 exomes AF: 0.0109 AC: 1918AN: 176182Hom.: 22 AF XY: 0.0128 AC XY: 818AN XY: 63886
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GnomAD4 exome AF: 0.0113 AC: 11232AN: 992994Hom.: 78 Cov.: 19 AF XY: 0.0130 AC XY: 3800AN XY: 293388
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GnomAD4 genome AF: 0.00891 AC: 1001AN: 112359Hom.: 16 Cov.: 23 AF XY: 0.00854 AC XY: 295AN XY: 34527
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 17, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2018 | This variant is associated with the following publications: (PMID: 28492530, 27884173, 12390976) - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at