NM_001127671.2(LIFR):c.2335+1G>A AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Nov 7, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001230974.1

Allele description [Variation Report for NM_001127671.2(LIFR):c.2335+1G>A]

NM_001127671.2(LIFR):c.2335+1G>A

Gene:
LIFR:LIF receptor subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5p13.1
Genomic location:
Preferred name:
NM_001127671.2(LIFR):c.2335+1G>A
HGVS:
  • NC_000005.10:g.38489077C>T
  • NG_011817.1:g.111329G>A
  • NM_001127671.2:c.2335+1G>AMANE SELECT
  • NM_001364297.1:c.2335+1G>A
  • NM_001364298.1:c.2335+1G>A
  • NM_002310.6:c.2335+1G>A
  • NC_000005.9:g.38489179C>T
  • NM_002310.5:c.2335+1G>A
Molecular consequence:
  • NM_001127671.2:c.2335+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001364297.1:c.2335+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001364298.1:c.2335+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_002310.6:c.2335+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001403476Invitaecriteria provided, single submitter
Likely pathogenic
(Nov 7, 2019)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Null leukemia inhibitory factor receptor (LIFR) mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome.

Dagoneau N, Scheffer D, Huber C, Al-Gazali LI, Di Rocco M, Godard A, Martinovic J, Raas-Rothschild A, Sigaudy S, Unger S, Nicole S, Fontaine B, Taupin JL, Moreau JF, Superti-Furga A, Le Merrer M, Bonaventure J, Munnich A, Legeai-Mallet L, Cormier-Daire V.

Am J Hum Genet. 2004 Feb;74(2):298-305. Epub 2004 Jan 21.

PubMed [citation]
PMID:
14740318
PMCID:
PMC1181927
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001403476.2

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

Description

This sequence change affects a donor splice site in intron 16 of the LIFR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs772217684, ExAC 0.006%). This variant has not been reported in the literature in individuals with LIFR-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LIFR are known to be pathogenic (PMID: 14740318). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: May 10, 2021

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