NM_018136.4(ASPM):c.4195dupA (p.Thr1399Asnfs) AND Primary autosomal recessive microcephaly 5

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 1, 2009
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000005252.4

Allele description

NM_018136.4(ASPM):c.4195dupA (p.Thr1399Asnfs)

Gene:

ASPM:abnormal spindle microtubule assembly [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_018136.4(ASPM):c.4195dupA (p.Thr1399Asnfs)

HGVS:

NC_000001.11:g.197105056dupT
NG_015867.1:g.46639dupA
NM_001206846.1:c.4066-8892dupA
NM_018136.4:c.4195dupA
NP_060606.3:p.Thr1399Asnfs
NC_000001.10:g.197074186dupT

Links:

OMIM: 605481.0009; dbSNP: rs199422163

NCBI 1000 Genomes Browser:

rs199422163

Molecular consequence:

NM_018136.4:c.4195dupA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001206846.1:c.4066-8892dupA - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Primary autosomal recessive microcephaly 5 (MCPH5)
Identifiers:: MedGen: C1837501; Orphanet: 2512; OMIM: 608716

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025430	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2008)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000041356	GeneReviews	no assertion criteria provided	pathologic (Sep 1, 2009)	not provided	curation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025430

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 2008)

germline

literature only

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

SCV000041356

GeneReviews

no assertion criteria provided

pathologic
(Sep 1, 2009)

not provided

curation

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	not provided	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Primary microcephaly with ASPM mutation shows simplified cortical gyration with antero-posterior gradient pre- and post-natally.

Desir J, Cassart M, David P, Van Bogaert P, Abramowicz M.

Am J Med Genet A. 2008 Jun 1;146A(11):1439-43. doi: 10.1002/ajmg.a.32312.

PubMed [citation]

PMID:: 18452193

Details of each submission

From OMIM, SCV000025430.3

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

Description

In 2 sibs, born of consanguineous Moroccan parents, with primary microcephaly-5 (MCPH5; 608716) and simplified gyration pattern on brain MRI, Desir et al. (2008) identified a homozygous 1-bp insertion (4195insA) in exon 18 of the ASPM gene, resulting in a frameshift and premature termination. The unaffected parents were heterozygous for the mutation. MRI in both patients showed that the simplified gyration was more severe in the anterior cortex. The data indicated that at least 1 form of primary microcephaly is allelic to a form of microcephaly with simplified gyral pattern (603802). However, Desir et al. (2008) noted that prenatal and postnatal brain imaging of patients with microcephaly has rarely been reported, suggesting that the 2 disorders may actually represent a phenotypic continuum. The findings also indicated that neuronal depletion of the ASPM gene predominantly affects the anterior cortex.

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

From GeneReviews, SCV000041356.1

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

Description

Converted during submission to Pathogenic.

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

Last Updated: Aug 31, 2018

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