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NM_005476.7(GNE):c.1740del (p.Cys581fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 9, 2020
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:
RCV001381213.14

Allele description [Variation Report for NM_005476.7(GNE):c.1740del (p.Cys581fs)]

NM_005476.7(GNE):c.1740del (p.Cys581fs)

Gene:
GNE:glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
9p13.3
Genomic location:
Preferred name:
NM_005476.7(GNE):c.1740del (p.Cys581fs)
HGVS:
  • NC_000009.12:g.36219915del
  • NG_008246.1:g.62131del
  • NM_001128227.3:c.1833del
  • NM_001190383.3:c.1518del
  • NM_001190384.3:c.1410del
  • NM_001190388.2:c.1563del
  • NM_001374797.1:c.1587del
  • NM_001374798.1:c.1563del
  • NM_005476.7:c.1740delMANE SELECT
  • NP_001121699.1:p.Cys612fs
  • NP_001177312.1:p.Cys507fs
  • NP_001177313.1:p.Cys471fs
  • NP_001177317.2:p.Cys522fs
  • NP_001361726.1:p.Cys530fs
  • NP_001361727.1:p.Cys522fs
  • NP_005467.1:p.Cys581fs
  • LRG_1197t1:c.1833del
  • LRG_1197t2:c.1740del
  • LRG_1197:g.62131del
  • LRG_1197p1:p.Cys612fs
  • LRG_1197p2:p.Cys581fs
  • NC_000009.11:g.36219911del
  • NC_000009.11:g.36219912del
  • NM_001128227.2:c.1833delC
  • NM_005476.5:c.1740del
Protein change:
C471fs
Links:
dbSNP: rs1554658453
NCBI 1000 Genomes Browser:
rs1554658453
Molecular consequence:
  • NM_001128227.3:c.1833del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001190383.3:c.1518del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001190384.3:c.1410del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001190388.2:c.1563del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001374797.1:c.1587del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001374798.1:c.1563del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_005476.7:c.1740del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
GNE myopathy (NM)
Synonyms:
Nonaka myopathy; Nonaka distal myopathy; INCLUSION BODY MYOPATHY, HEREDITARY, AUTOSOMAL RECESSIVE; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011603; MedGen: C1853926; Orphanet: 602; OMIM: 605820
Name:
Sialuria
Synonyms:
Sialic Acid Storage Disease; Sialuria, French type
Identifiers:
MONDO: MONDO:0010028; MedGen: C0342853; Orphanet: 3166; OMIM: 269921

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001579516Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 9, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Heterozygous UDP-GlcNAc 2-epimerase and N-acetylmannosamine kinase domain mutations in the GNE gene result in a less severe GNE myopathy phenotype compared to homozygous N-acetylmannosamine kinase domain mutations.

Mori-Yoshimura M, Monma K, Suzuki N, Aoki M, Kumamoto T, Tanaka K, Tomimitsu H, Nakano S, Sonoo M, Shimizu J, Sugie K, Nakamura H, Oya Y, Hayashi YK, Malicdan MC, Noguchi S, Murata M, Nishino I.

J Neurol Sci. 2012 Jul 15;318(1-2):100-5. doi: 10.1016/j.jns.2012.03.016. Epub 2012 Apr 14.

PubMed [citation]
PMID:
22507750

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001579516.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the GNE protein. Other variant(s) that disrupt this region (p.Cys617Alafs*57) have been determined to be pathogenic (PMID: 22507750, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with GNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 551069). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the GNE gene (p.Cys612Valfs*62). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 142 amino acid(s) of the GNE protein.

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

Last Updated: Nov 10, 2024