U.S. flag

An official website of the United States government

NM_000232.5(SGCB):c.-10_22dup (p.Ala8fs) AND Autosomal recessive limb-girdle muscular dystrophy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 1, 2021
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:
RCV001778998.1

Allele description [Variation Report for NM_000232.5(SGCB):c.-10_22dup (p.Ala8fs)]

NM_000232.5(SGCB):c.-10_22dup (p.Ala8fs)

Genes:
LOC129992585:ATAC-STARR-seq lymphoblastoid silent region 15421 [Gene]
SGCB:sarcoglycan beta [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
4q12
Genomic location:
Preferred name:
NM_000232.5(SGCB):c.-10_22dup (p.Ala8fs)
HGVS:
  • NC_000004.12:g.52038250_52038281dup
  • NG_008891.1:g.5051_5082dup
  • NM_000232.5:c.-10_22dupMANE SELECT
  • NP_000223.1:p.Ala8fs
  • NP_000223.1:p.Ala8fs
  • LRG_204t1:c.-10_22dup
  • LRG_204:g.5051_5082dup
  • LRG_204p1:p.Ala8fs
  • NC_000004.11:g.52904403_52904404insCCGCCGCCGCCGCTGCCGCCATCTTCCCGCGC
  • NC_000004.11:g.52904416_52904447dup
  • NM_000232.4:c.-10_22dup
  • NM_000232.4:c.-10_22dup32
Protein change:
A8fs
Links:
dbSNP: rs1553940963
NCBI 1000 Genomes Browser:
rs1553940963
Molecular consequence:
  • NM_000232.5:c.-10_22dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_000232.5:c.-10_22dup - initiator_codon_variant - [Sequence Ontology: SO:0001582]

Condition(s)

Name:
Autosomal recessive limb-girdle muscular dystrophy
Identifiers:
MONDO: MONDO:0015152; MedGen: C2931907; OMIM: PS253600

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002015074Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(Oct 1, 2021)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel sarcoglycan gene mutations in a large cohort of Italian patients.

Boito C, Fanin M, Siciliano G, Angelini C, Pegoraro E.

J Med Genet. 2003 May;40(5):e67. No abstract available.

PubMed [citation]
PMID:
12746421
PMCID:
PMC1735456

Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E.

Semplicini C, Vissing J, Dahlqvist JR, Stojkovic T, Bello L, Witting N, Duno M, Leturcq F, Bertolin C, D'Ambrosio P, Eymard B, Angelini C, Politano L, LaforĂȘt P, Pegoraro E.

Neurology. 2015 Apr 28;84(17):1772-81. doi: 10.1212/WNL.0000000000001519. Epub 2015 Apr 10.

PubMed [citation]
PMID:
25862795
PMCID:
PMC4424130

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002015074.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: SGCB c.-10_22dup32 is located in the untranslated mRNA region upstream and the coding region including the initiation codon.The variant was absent in 37246 control chromosomes (gnomAD v2), however, it is found in 9/150846 controls in gnomAD v3. c.-10_22dup32 has been reported in the literature in multiple individuals affected with mild Limb-Girdle Muscular Dystrophy in homozygous state (Boito_2003, Semplicini_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. This variant is predicted to result in p.Ala8Glyfs*22 if the first initiation codon is utilized for translation. However, biochemical data of residual sarcoglycan expression in skeletal muscle and mild phenotype in variant carriers suggest that the second initiation codon in the mutant gene may also be utilized, which results in a normal protein (Semplicini_2015). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Although this variant has been found in mutliple patients, due to lack of functional evidence, the variant was classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024