NM_004543.4:c.7432-2025_7536+372del2502

NM_004543.4:c.7432-2025_7536+372del2502

Variant type:
Deletion
Cytogenetic location:
2q23
Genomic location:
  • Chr2:152502272 - 152504773 (on Assembly GRCh37)
  • Chr2:151645758 - 151648259 (on Assembly GRCh38)
HGVS:
  • NG_009382.2:g.91229_93730del2502
  • NM_004543.4:c.7432-2025_7536+372del2502
  • NC_000002.12:g.151645758_151648259del2502 (GRCh38)
  • NC_000002.11:g.152502272_152504773del2502 (GRCh37)
  • LRG_202:g.91229_93730del2502
  • NM_004543.3:c.7432-2025_7536+372del2502
Links:
NCBI 1000 Genomes Browser:
rs80358246

Clinical significance

NM_004543.4:c.7432-2025_7536+372del2502

Clinical significance:
Pathogenic/Likely pathogenic
Review status:
2 stars out of maximum of 4 stars
classified by multiple submitters
Number of submission(s):
2
Condition(s)
See supporting ClinVar records

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Recent Activity

Assertion and evidence details

Germline

Clinical significance
(Last evaluated)
Review status
(Assertion method)
Collection methodCondition(s)
(Mode of inheritance)
OriginCitationsSubmitter
(Last submitted)
Submission accession
Pathogenic
(Sep 17, 2013)
classified by single submitter
(literature only)
literature onlygermlinePubMed (3)
OMIM
(Dec 30, 2010)
SCV000035353
Pathogenic
(Mar 15, 2012)
classified by single submitter
(literature only)
literature onlynot providedPubMed (2)
GeneReviews
(Apr 30, 2013)
SCV000041104

Summary

FamiliesIndividualsSegregationAllele originEthnicityGeographic origin
not providednot providednot providedgermline, not providednot providednot provided

GeneReviews

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providednot provided

OMIM

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providedgermline

Description

In 5 affected individuals from 5 Ashkenazi Jewish families with autosomal recessive typical nemaline myopathy (256030), Anderson et al. (2004) identified a 2,502-bp deletion completely encompassing exon 55 and parts of introns 54 and 55 of the NEB gene, predicted to result in a transcript encoding 35 fewer amino acids. Screening for this mutation in a random sample of 4,090 Ashkenazi Jewish individuals revealed a carrier frequency of 1 in 108.
Lehtokari et al. (2009) identified the 2,502-bp deletion in 14 of 355 probands with nemaline myopathy from around the world; 2 of the probands had been reported by Anderson et al. (2004). Seven probands were homozygous for the deletion, and 7 carried the mutation in heterozygosity. Two of the families were not of known Ashkenazi Jewish descent, but carried the common haplotype identified in Ashkenazi Jews. The findings were consistent with a founder effect.
Ottenheijm et al. (2009) studied the muscular phenotype of nemaline myopathy patients with NEB exon 55 deletion (NM-NEB). SDS-PAGE and Western blot analysis revealed greatly reduced nebulin levels in skeletal muscle of NM-NEB patients, with the most prominent reduction at nebulin's N-terminal end. Muscle mechanical studies indicated an approximately 60% reduced force generating capacity of NM-NEB muscle and a leftward shift of the force-sarcomere length relation in NM-NEB muscle fibers. This indicates that the mechanism for the force reduction is likely to include shorter and nonuniform thin filament lengths in NM-NEB muscle compared with control muscle. The average thin filament length was reduced from approximately 1.3-micrometer in control muscle to approximately 0.75-micrometer in NM-NEB muscle. Ottenheijm et al. (2009) hypothesized that dysregulated thin filament length may contribute to muscle weakness in nemaline myopathy patients with nebulin mutations.

Last Updated: Dec 14, 2014

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