rs587783560
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PM5PP3_ModeratePP5_Very_Strong
The NM_001195553.2(DCX):c.538A>G(p.Lys180Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K180N) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001195553.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCX | NM_001195553.2 | c.538A>G | p.Lys180Glu | missense_variant | 3/7 | ENST00000636035.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCX | ENST00000636035.2 | c.538A>G | p.Lys180Glu | missense_variant | 3/7 | 2 | NM_001195553.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 24
ClinVar
Submissions by phenotype
Ectopic tissue Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 30, 2022 | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DCX protein function. ClinVar contains an entry for this variant (Variation ID: 158474). This missense change has been observed in individual(s) with lissencephaly and subcortical band heterotopia (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 180 of the DCX protein (p.Lys180Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at