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NM_006946.4(SPTBN2):c.1310G>A (p.Arg437Gln) AND Spinocerebellar ataxia type 5

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Sep 1, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000677650.4

Allele description [Variation Report for NM_006946.4(SPTBN2):c.1310G>A (p.Arg437Gln)]

NM_006946.4(SPTBN2):c.1310G>A (p.Arg437Gln)

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.1310G>A (p.Arg437Gln)
HGVS:
  • NC_000011.10:g.66708181C>T
  • NG_016150.2:g.26181G>A
  • NM_006946.4:c.1310G>AMANE SELECT
  • NP_008877.2:p.Arg437Gln
  • NC_000011.9:g.66475652C>T
  • NM_006946.2:c.1310G>A
Protein change:
R437Q
Links:
dbSNP: rs1554986337
NCBI 1000 Genomes Browser:
rs1554986337
Molecular consequence:
  • NM_006946.4:c.1310G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000803781Equipe Genetique des Anomalies du Developpement, Université de Bourgogne - Clinvar_gadteam_Clinical_exome_analysis_3
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Oct 11, 2017)
de novoclinical testing

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

SCV0025728393billion
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Sep 1, 2022)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyes1not providednot provided1not providedclinical testing

Citations

PubMed

Clinical application of whole-exome sequencing across clinical indications.

Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F, Vertino-Bell A, Smaoui N, Neidich J, Monaghan KG, McKnight D, Bai R, Suchy S, Friedman B, Tahiliani J, Pineda-Alvarez D, Richard G, Brandt T, Haverfield E, Chung WK, Bale S.

Genet Med. 2016 Jul;18(7):696-704. doi: 10.1038/gim.2015.148. Epub 2015 Dec 3.

PubMed [citation]
PMID:
26633542

Heterozygous missense variants of SPTBN2 are a frequent cause of congenital cerebellar ataxia.

Nicita F, Nardella M, Bellacchio E, Alfieri P, Terrone G, Piccini G, Graziola F, Pignata C, Capuano A, Bertini E, Zanni G.

Clin Genet. 2019 Aug;96(2):169-175. doi: 10.1111/cge.13562. Epub 2019 Jun 5.

PubMed [citation]
PMID:
31066025
See all PubMed Citations (3)

Details of each submission

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne - Clinvar_gadteam_Clinical_exome_analysis_3, SCV000803781.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

From 3billion, SCV002572839.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000546676). The variant has been previously reported as de novo in a similarly affected individual (PMID: 31066025). Different missense changes at the same codon (p.Arg437Gly, p.Arg437Trp) have been reported to be associated with SPTBN2-related disorder (ClinVar ID: VCV000928964 / PMID: 26633542 , 31066025). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Oct 20, 2024