NM_001195553.2(DCX):c.665C>T (p.Thr222Ile) AND Lissencephaly type 1 due to doublecortin gene mutation

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 15, 2018
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:: RCV000984506.2

Allele description [Variation Report for NM_001195553.2(DCX):c.665C>T (p.Thr222Ile)]

NM_001195553.2(DCX):c.665C>T (p.Thr222Ile)

Gene:

DCX:doublecortin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq23

Genomic location:

Preferred name:

NM_001195553.2(DCX):c.665C>T (p.Thr222Ile)

HGVS:

NC_000023.11:g.111401030G>A
NG_011750.1:g.16149C>T
NM_000555.3:c.908C>T
NM_001195553.2:c.665C>TMANE SELECT
NM_001369370.1:c.665C>T
NM_001369371.1:c.665C>T
NM_001369372.1:c.665C>T
NM_001369373.1:c.665C>T
NM_001369374.1:c.665C>T
NM_178151.3:c.665C>T
NM_178152.3:c.665C>T
NM_178153.3:c.665C>T
NP_000546.2:p.Thr303Ile
NP_001182482.1:p.Thr222Ile
NP_001356299.1:p.Thr222Ile
NP_001356300.1:p.Thr222Ile
NP_001356301.1:p.Thr222Ile
NP_001356302.1:p.Thr222Ile
NP_001356303.1:p.Thr222Ile
NP_835364.1:p.Thr222Ile
NP_835365.1:p.Thr222Ile
NP_835366.1:p.Thr222Ile
NC_000023.10:g.110644258G>A
p.Thr303Ile

Protein change:

T222I

Links:

dbSNP: rs1603423268

NCBI 1000 Genomes Browser:

rs1603423268

Molecular consequence:

NM_000555.3:c.908C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195553.2:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369370.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369371.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369372.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369373.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369374.1:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_178151.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_178152.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_178153.3:c.665C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001132562	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 15, 2018)	de novo	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001132562

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 15, 2018)

de novo

research

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	research

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001132562.1

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

Description

The hemizygous p.Thr303Ile variant in DCX was identified by our study in one individual with Lissencephaly. Trio exome analysis showed this variant to be de novo. This variant was absent from large population studies. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic.

#	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: May 26, 2024

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