NM_001195553.2(DCX):c.304C>A (p.Arg102Ser) AND Lissencephaly type 1 due to doublecortin gene mutation

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 2, 2021
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:: RCV001775265.1

Allele description [Variation Report for NM_001195553.2(DCX):c.304C>A (p.Arg102Ser)]

NM_001195553.2(DCX):c.304C>A (p.Arg102Ser)

Gene:

DCX:doublecortin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq23

Genomic location:

Preferred name:

NM_001195553.2(DCX):c.304C>A (p.Arg102Ser)

HGVS:

NC_000023.11:g.111410095G>T
NG_011750.1:g.7084C>A
NM_000555.3:c.547C>A
NM_001195553.2:c.304C>AMANE SELECT
NM_001369370.1:c.304C>A
NM_001369371.1:c.304C>A
NM_001369372.1:c.304C>A
NM_001369373.1:c.304C>A
NM_001369374.1:c.304C>A
NM_178151.3:c.304C>A
NM_178152.3:c.304C>A
NM_178153.3:c.304C>A
NP_000546.2:p.Arg183Ser
NP_001182482.1:p.Arg102Ser
NP_001356299.1:p.Arg102Ser
NP_001356300.1:p.Arg102Ser
NP_001356301.1:p.Arg102Ser
NP_001356302.1:p.Arg102Ser
NP_001356303.1:p.Arg102Ser
NP_835364.1:p.Arg102Ser
NP_835365.1:p.Arg102Ser
NP_835366.1:p.Arg102Ser
NC_000023.10:g.110653323G>T
NM_178151.2:c.304C>A

Protein change:

R102S

Links:

dbSNP: rs587783541

NCBI 1000 Genomes Browser:

rs587783541

Molecular consequence:

NM_000555.3:c.547C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195553.2:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369370.1:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369371.1:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369372.1:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369373.1:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369374.1:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178151.3:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178152.3:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178153.3:c.304C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Lissencephaly type 1 due to doublecortin gene mutation
Synonyms:: LISSENCEPHALY, X-LINKED, 1; Lissencephaly, X-linked; 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
SCV002011995	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 2, 2021)	germline	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

SCV002011995

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 2, 2021)

germline

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	germline	yes	1	not provided	not provided	1	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 3billion, SCV002011995.1

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

Description

The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Arg102Gly and p.Arg102His) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000280251.2 and VCV000082052.8 PM5). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.983, 3Cnet: 0.999, PP3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Dec 24, 2023

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