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NM_030650.3(LNPK):c.751C>T (p.Arg251Ter) AND Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 17, 2018
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000677384.1

Allele description [Variation Report for NM_030650.3(LNPK):c.751C>T (p.Arg251Ter)]

NM_030650.3(LNPK):c.751C>T (p.Arg251Ter)

Gene:
LNPK:lunapark, ER junction formation factor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.1
Genomic location:
Preferred name:
NM_030650.3(LNPK):c.751C>T (p.Arg251Ter)
HGVS:
  • NC_000002.12:g.175939613G>A
  • NM_001305008.1:c.949C>T
  • NM_001305009.1:c.844C>T
  • NM_001305010.1:c.757C>T
  • NM_001305011.2:c.382C>T
  • NM_030650.3:c.751C>TMANE SELECT
  • NP_001291937.1:p.Arg317Ter
  • NP_001291938.1:p.Arg282Ter
  • NP_001291939.1:p.Arg253Ter
  • NP_001291940.1:p.Arg128Ter
  • NP_085153.1:p.Arg251Ter
  • NC_000002.11:g.176804341G>A
  • NM_030650.2:c.751C>T
  • NR_130941.2:n.1269C>T
Protein change:
R128*; ARG251TER
Links:
OMIM: 610236.0002; dbSNP: rs1391644554
NCBI 1000 Genomes Browser:
rs1391644554
Molecular consequence:
  • NR_130941.2:n.1269C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001305008.1:c.949C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001305009.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001305010.1:c.757C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001305011.2:c.382C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_030650.3:c.751C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum
Identifiers:
MONDO: MONDO:0060761; MedGen: C4748137; OMIM: 618090

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000803647OMIM
no assertion criteria provided
Pathogenic
(Aug 17, 2018) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in LNPK, Encoding the Endoplasmic Reticulum Junction Stabilizer Lunapark, Cause a Recessive Neurodevelopmental Syndrome.

Breuss MW, Nguyen A, Song Q, Nguyen T, Stanley V, James KN, Musaev D, Chai G, Wirth SA, Anzenberg P, George RD, Johansen A, Ali S, Zia-Ur-Rehman M, Sultan T, Zaki MS, Gleeson JG.

Am J Hum Genet. 2018 Aug 2;103(2):296-304. doi: 10.1016/j.ajhg.2018.06.011. Epub 2018 Jul 19.

PubMed [citation]
PMID:
30032983
PMCID:
PMC6080764

Details of each submission

From OMIM, SCV000803647.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 13.5-year-old girl, born of consanguineous Pakistani parents (family B), with neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum (NEDEHCC; 618090), Breuss et al. (2018) identified a homozygous c.751C-T transition (c.751C-T, NM_030650.2) in exon 10 of the LNPK gene, resulting in an arg251-to-ter (R251X) substitution. The mutation was predicted to result in truncation of the gene product after the transmembrane domain but before the zinc finger domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the ExAC or gnomAD databases or in 5,000 in-house control individuals. Patient fibroblasts showed reduction of LNPK mRNA and no evidence of the full-length or a truncated protein. However, expression of the mutation in HEK293 cells showed a punctate pattern reminiscent of wildtype, and the truncated protein had increased stability compared to wildtype. Breuss et al. (2018) suggested that loss of protein function was the most likely pathogenic mechanism, but could not exclude the contribution of a truncated protein.

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

Last Updated: Apr 23, 2022