NM_006946.4(SPTBN2):c.758T>C (p.Leu253Pro) AND Spinocerebellar ataxia type 5

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 15, 2010
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:: RCV000005593.4

Allele description [Variation Report for NM_006946.4(SPTBN2):c.758T>C (p.Leu253Pro)]

NM_006946.4(SPTBN2):c.758T>C (p.Leu253Pro)

Gene:

SPTBN2:spectrin beta, non-erythrocytic 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_006946.4(SPTBN2):c.758T>C (p.Leu253Pro)

HGVS:

NC_000011.10:g.66713645A>G
NG_016150.2:g.20717T>C
NM_006946.4:c.758T>CMANE SELECT
NP_008877.2:p.Leu253Pro
NC_000011.9:g.66481116A>G
O15020:p.Leu253Pro

Protein change:

L253P; LEU253PRO

Links:

UniProtKB: O15020#VAR_026767; OMIM: 604985.0003; dbSNP: rs121918306

Molecular consequence:

NM_006946.4:c.758T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spinocerebellar ataxia type 5 (SCA5)
Identifiers:: MONDO: MONDO:0010848; MedGen: C0752123; Orphanet: 98766; OMIM: 600224

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025775	OMIM	no assertion criteria provided	Pathogenic (Sep 15, 2010)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 16429157, 20603325

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025775

OMIM

no assertion criteria provided

Pathogenic
(Sep 15, 2010)

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

Spectrin mutations cause spinocerebellar ataxia type 5.

Ikeda Y, Dick KA, Weatherspoon MR, Gincel D, Armbrust KR, Dalton JC, Stevanin G, Dürr A, Zühlke C, Bürk K, Clark HB, Brice A, Rothstein JD, Schut LJ, Day JW, Ranum LP.

Nat Genet. 2006 Feb;38(2):184-90. Epub 2006 Jan 22.

PubMed [citation]

PMID:: 16429157

Beta-III spectrin mutation L253P associated with spinocerebellar ataxia type 5 interferes with binding to Arp1 and protein trafficking from the Golgi.

Clarkson YL, Gillespie T, Perkins EM, Lyndon AR, Jackson M.

Hum Mol Genet. 2010 Sep 15;19(18):3634-41. doi: 10.1093/hmg/ddq279. Epub 2010 Jul 5.

PubMed [citation]

PMID:: 20603325
PMCID:: PMC2928133

Details of each submission

From OMIM, SCV000025775.2

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

Description

In a German family, Ikeda et al. (2006) found that spinocerebellar ataxia (SCA5; 600224) was related to a T-to-C transition (758T-C) in exon 7 of the SPTBN2 gene that caused a leucine-to-proline change (L253P) in the calponin homology domain containing the actin/ARP1 (see 605143)-binding site.

Clarkson et al. (2010) introduced the L253P mutation into rat Spnb3 and found that the mutant protein was not targeted to the plasma membrane of transfected cells but was retained in the Golgi compartment. Mutant Spnb3 did not interact with Arp1 (605143), prevented correct localization of the wildtype protein, and caused Golgi accumulation of Eaat4 (600637), preventing it from reaching the plasma membrane. These data provided evidence for a dominant-negative effect of the mutation.

#	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 12, 2026

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