NM_001195553.2(DCX):c.907C>T (p.Arg303Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 27, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000493373.10

Allele description [Variation Report for NM_001195553.2(DCX):c.907C>T (p.Arg303Ter)]

NM_001195553.2(DCX):c.907C>T (p.Arg303Ter)

Gene:

DCX:doublecortin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq23

Genomic location:

Preferred name:

NM_001195553.2(DCX):c.907C>T (p.Arg303Ter)

HGVS:

NC_000023.11:g.111330943G>A
NG_011750.1:g.86236C>T
NM_000555.3:c.1150C>T
NM_001195553.2:c.907C>TMANE SELECT
NM_001369370.1:c.907C>T
NM_001369371.1:c.907C>T
NM_001369372.1:c.907C>T
NM_001369373.1:c.907C>T
NM_001369374.1:c.907C>T
NM_178151.3:c.907C>T
NM_178152.3:c.907C>T
NM_178153.3:c.907C>T
NP_000546.2:p.Arg384Ter
NP_001182482.1:p.Arg303Ter
NP_001356299.1:p.Arg303Ter
NP_001356300.1:p.Arg303Ter
NP_001356301.1:p.Arg303Ter
NP_001356302.1:p.Arg303Ter
NP_001356303.1:p.Arg303Ter
NP_835364.1:p.Arg303Ter
NP_835364.1:p.Arg303Ter
NP_835365.1:p.Arg303Ter
NP_835366.1:p.Arg303Ter
NC_000023.10:g.110574171G>A
NM_001195553.2:c.907C>T
NM_178151.2:c.907C>T
NM_178153.1:c.907C>T

Protein change:

R303*

Links:

dbSNP: rs587783592

NCBI 1000 Genomes Browser:

rs587783592

Molecular consequence:

NM_000555.3:c.1150C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001195553.2:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369370.1:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369371.1:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369372.1:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369373.1:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369374.1:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_178151.3:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_178152.3:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_178153.3:c.907C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000582782	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 12, 2020)	germline	clinical testing	Citation Link,
SCV002231678	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11175293, 23365099, 10369164, 29671837, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000582782

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Oct 12, 2020)

germline

clinical testing

Citation Link,

SCV002231678

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

germline

clinical testing

PubMed (5)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia.

Matsumoto N, Leventer RJ, Kuc JA, Mewborn SK, Dudlicek LL, Ramocki MB, Pilz DT, Mills PL, Das S, Ross ME, Ledbetter DH, Dobyns WB.

Eur J Hum Genet. 2001 Jan;9(1):5-12.

PubMed [citation]

PMID:: 11175293

New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum.

Bahi-Buisson N, Souville I, Fourniol FJ, Toussaint A, Moores CA, Houdusse A, Lemaitre JY, Poirier K, Khalaf-Nazzal R, Hully M, Leger PL, Elie C, Boddaert N, Beldjord C, Chelly J, Francis F; SBH-LIS European Consortium.

Brain. 2013 Jan;136(Pt 1):223-44. doi: 10.1093/brain/aws323.

PubMed [citation]

PMID:: 23365099
PMCID:: PMC3562079

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000582782.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 10807542, 9618162, 10369164, 11175293, 23365099, 29671837, 32978145)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231678.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg303*) in the DCX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DCX are known to be pathogenic (PMID: 11175293, 23365099). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with lissencephaly and subcortical band heterotopia (PMID: 10369164, 29671837). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 158511). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 20, 2024

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