NM_004849.4(ATG5):c.366A>T (p.Glu122Asp) AND Spinocerebellar ataxia, autosomal recessive 25

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 1, 2005
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:: RCV000496077.2

Allele description [Variation Report for NM_004849.4(ATG5):c.366A>T (p.Glu122Asp)]

NM_004849.4(ATG5):c.366A>T (p.Glu122Asp)

Gene:

ATG5:autophagy related 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q21

Genomic location:

Preferred name:

NM_004849.4(ATG5):c.366A>T (p.Glu122Asp)

HGVS:

NC_000006.12:g.106279773T>A
NM_001286106.2:c.366A>T
NM_001286107.2:c.132A>T
NM_001286108.2:c.366A>T
NM_001286111.2:c.109-31529A>T
NM_004849.4:c.366A>TMANE SELECT
NP_001273035.1:p.Glu122Asp
NP_001273036.1:p.Glu44Asp
NP_001273037.1:p.Glu122Asp
NP_004840.1:p.Glu122Asp
NC_000006.11:g.106727648T>A
NM_004849.2:c.366A>T
NR_104402.1:n.424A>T
NR_104403.1:n.296A>T

Protein change:

E122D; GLU122ASP

Links:

OMIM: 604261.0001; dbSNP: rs1131692265

NCBI 1000 Genomes Browser:

rs1131692265

Molecular consequence:

NM_001286111.2:c.109-31529A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001286106.2:c.366A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001286107.2:c.132A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001286108.2:c.366A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004849.4:c.366A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104402.1:n.424A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104403.1:n.296A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Spinocerebellar ataxia, autosomal recessive 25
Identifiers:: MONDO: MONDO:0033115; MedGen: C4539808; OMIM: 617584

Recent activity

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Chain C, Small ribosomal subunit protein uS3
Chain C, Small ribosomal subunit protein uS3
gi|2557041383|pdb|8CA7|C

Protein
Chain A, 16S rRNA
Chain A, 16S rRNA
gi|2557041382|pdb|8CA7|A

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000584049	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2005)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 26812546, 15981765

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000584049

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2005)

germline

literature only

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay.

Kim M, Sandford E, Gatica D, Qiu Y, Liu X, Zheng Y, Schulman BA, Xu J, Semple I, Ro SH, Kim B, Mavioglu RN, Tolun A, Jipa A, Takats S, Karpati M, Li JZ, Yapici Z, Juhasz G, Lee JH, Klionsky DJ, Burmeister M.

Elife. 2016 Jan 26;5. doi:pii: e12245. 10.7554/eLife.12245.

PubMed [citation]

PMID:: 26812546
PMCID:: PMC4786408

Non-progressive congenital ataxia with cerebellar hypoplasia in three families.

Yapici Z, Eraksoy M.

Acta Paediatr. 2005 Feb;94(2):248-53. Review.

PubMed [citation]

PMID:: 15981765

Details of each submission

From OMIM, SCV000584049.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In 2 brothers, born of remotely consanguineous Turkish parents, with autosomal recessive spinocerebellar ataxia-25 (SCAR25; 617584), Kim et al. (2016) identified a homozygous c.648T-A transversion (chr6.106,727,648T-A, GRCh37) in the ATG5 gene, resulting in a glu122-to-asp (E122D) substitution at a highly conserved residue in the vicinity of the interaction between ATG5 and ATG12 (609608). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutation was not found in the 1000 Genomes Project, Exome Variant Server, or ExAC databases, or in 500 Turkish control samples. Patient cells showed a reduced interaction between ATG5 and ATG12 and impaired autophagic flux compared to controls. In vitro functional expression studies showed that the E122D mutant protein had normal expression levels, but impaired interaction with ATG12; interaction with ATG16L was not impaired. The findings were consistent with E122D being a hypomorphic allele. The family was originally reported by Yapici and Eraksoy (2005).

#	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

Last Updated: Apr 23, 2022

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