NM_001195553.2(DCX):c.4G>A (p.Glu2Lys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003560297.2

Allele description [Variation Report for NM_001195553.2(DCX):c.4G>A (p.Glu2Lys)]

NM_001195553.2(DCX):c.4G>A (p.Glu2Lys)

Gene:

DCX:doublecortin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq23

Genomic location:

Preferred name:

NM_001195553.2(DCX):c.4G>A (p.Glu2Lys)

HGVS:

NC_000023.11:g.111410395C>T
NG_011750.1:g.6784G>A
NM_000555.3:c.247G>A
NM_001195553.2:c.4G>AMANE SELECT
NM_001369370.1:c.4G>A
NM_001369371.1:c.4G>A
NM_001369372.1:c.4G>A
NM_001369373.1:c.4G>A
NM_001369374.1:c.4G>A
NM_001410715.1:c.4G>A
NM_178151.3:c.4G>A
NM_178152.3:c.4G>A
NM_178153.3:c.4G>A
NP_000546.2:p.Glu83Lys
NP_001182482.1:p.Glu2Lys
NP_001356299.1:p.Glu2Lys
NP_001356300.1:p.Glu2Lys
NP_001356301.1:p.Glu2Lys
NP_001356302.1:p.Glu2Lys
NP_001356303.1:p.Glu2Lys
NP_001397644.1:p.Glu2Lys
NP_835364.1:p.Glu2Lys
NP_835365.1:p.Glu2Lys
NP_835366.1:p.Glu2Lys
NC_000023.10:g.110653623C>T

Protein change:

E2K

Molecular consequence:

NM_000555.3:c.247G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195553.2:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369370.1:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369371.1:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369372.1:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369373.1:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369374.1:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001410715.1:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178151.3:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178152.3:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178153.3:c.4G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004298970	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20726879, 30979500, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298970

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Familial Lennox-Gastaut syndrome in male siblings with a novel DCX mutation and anterior pachygyria.

Lawrence KM, Mei D, Newton MR, Leventer RJ, Guerrini R, Berkovic SF.

Epilepsia. 2010 Sep;51(9):1902-5. doi: 10.1111/j.1528-1167.2010.02694.x.

PubMed [citation]

PMID:: 20726879

Pathogenic E2K mutation of doublecortin X (DCX) alters microtubule stabilisation and actin filament association.

Moslehi M, Ng DCH, Bogoyevitch MA.

Biochem Biophys Res Commun. 2019 Jun 4;513(3):540-545. doi: 10.1016/j.bbrc.2019.04.005. Epub 2019 Apr 9.

PubMed [citation]

PMID:: 30979500

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298970.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This missense change has been observed in individual(s) with DCX-related conditions (PMID: 20726879). It has also been observed to segregate with disease in related individuals. Experimental studies have shown that this missense change affects DCX function (PMID: 30979500). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2 of the DCX protein (p.Glu2Lys).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine