NM_001195553.2(DCX):c.907C>T (p.Arg303Ter) AND Lissencephaly type 1 due to doublecortin gene mutation

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 23, 2024
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:: RCV003326123.5

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)

Name:: Lissencephaly type 1 due to doublecortin gene mutation
Synonyms:: LISSENCEPHALY, X-LINKED, 1; Lissencephaly and agenesis of corpus callosum
Identifiers:: MONDO: MONDO:0010239; MedGen: C4551968; Orphanet: 2148; OMIM: 300067

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004032232	Pediatric Department, Xiangya Hospital, Central South University	no assertion criteria provided (ACMG Guidelines, 2015)	Pathogenic	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV004047210	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005368387	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 23, 2024)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004032232

Pediatric Department, Xiangya Hospital, Central South University

no assertion criteria provided

(ACMG Guidelines, 2015)

Pathogenic

de novo

research

PubMed (1)
[See all records that cite this PMID]

SCV004047210

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005368387

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 23, 2024)

de novo

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Pediatric Department, Xiangya Hospital, Central South University, SCV004032232.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047210.1

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

Description

The premature translational stop signal (c.907C>T) variant has been reported previously in patients affected with lissencephaly and subcortical band heterotopia (Di Donato et. al., 2018). The c.907C>T variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change c.907C>T in DCX is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This stop gained (p.Arg303Ter) variant is expected to result in an absent or disrupted protein products and loss of function variants in DCX are known to be Pathogenic (Bahi-Buisson et. al., 2013; Matsumoto et. al., 2001). 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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV005368387.1

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

Description

Criteria applied: PVS1,PS2_VSTR,PS4_MOD,PM2

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

Last Updated: Oct 20, 2024

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