NM_006796.3(AFG3L2):c.1961C>T (p.Thr654Ile) AND Spinocerebellar ataxia type 28

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 11, 2019
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:: RCV000031941.7

Allele description [Variation Report for NM_006796.3(AFG3L2):c.1961C>T (p.Thr654Ile)]

NM_006796.3(AFG3L2):c.1961C>T (p.Thr654Ile)

Gene:

AFG3L2:AFG3 like matrix AAA peptidase subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18p11.21

Genomic location:

Preferred name:

NM_006796.3(AFG3L2):c.1961C>T (p.Thr654Ile)

HGVS:

NC_000018.10:g.12340220G>A
NG_023361.1:g.42057C>T
NM_006796.3:c.1961C>TMANE SELECT
NP_006787.2:p.Thr654Ile
NP_006787.2:p.Thr654Ile
LRG_666t1:c.1961C>T
LRG_666:g.42057C>T
LRG_666p1:p.Thr654Ile
NC_000018.9:g.12340219G>A
NM_006796.2:c.1961C>T
Q9Y4W6:p.Thr654Ile

Protein change:

T654I; THR654ILE

Links:

UniProtKB: Q9Y4W6#VAR_064402; OMIM: 604581.0009; dbSNP: rs151344513

NCBI 1000 Genomes Browser:

rs151344513

Molecular consequence:

NM_006796.3:c.1961C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spinocerebellar ataxia type 28 (SCA28)
Identifiers:: MONDO: MONDO:0012450; MedGen: C1853249; Orphanet: 101109; OMIM: 610246

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000044670	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 2010)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001190266	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 11, 2019)	unknown	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

SCV000044670

OMIM

no assertion criteria provided

Pathogenic
(Oct 1, 2010)

germline

literature only

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

SCV001190266

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 11, 2019)

unknown

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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Missense mutations in the AFG3L2 proteolytic domain account for ∼1.5% of European autosomal dominant cerebellar ataxias.

Cagnoli C, Stevanin G, Brussino A, Barberis M, Mancini C, Margolis RL, Holmes SE, Nobili M, Forlani S, Padovan S, Pappi P, Zaros C, Leber I, Ribai P, Pugliese L, Assalto C, Brice A, Migone N, Dürr A, Brusco A.

Hum Mutat. 2010 Oct;31(10):1117-24. doi: 10.1002/humu.21342.

PubMed [citation]

PMID:: 20725928

Facile, rapid, and large-area periodic patterning of semiconductor substrates with submicron inorganic structures.

Kempa TJ, Bediako DK, Jones EC, Lieber CM, Nocera DG.

J Am Chem Soc. 2015 Mar 25;137(11):3739-42. doi: 10.1021/ja5118717. Epub 2015 Mar 12.

PubMed [citation]

PMID:: 25741869

Details of each submission

From OMIM, SCV000044670.3

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

Description

In affected members of 2 unrelated families with autosomal dominant spinocerebellar ataxia-28 (SCA28; 610246), Cagnoli et al. (2010) identified a heterozygous 1961C-T transition in exon 15 of the AFG3L2 gene, resulting in a thr654-to-ile (T654I) substitution in a highly conserved residue in the C-terminal proteolytic peptidase-M41 domain. Haplotype analysis indicated a founder effect. The mutation was not identified in 380 French or Italian control chromosomes.

#	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 Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV001190266.1

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

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

Last Updated: Dec 24, 2023

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