NM_001127671.2(LIFR):c.756dup (p.Lys253Ter) AND Stuve-Wiedemann syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 17, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001809981.4

Allele description [Variation Report for NM_001127671.2(LIFR):c.756dup (p.Lys253Ter)]

NM_001127671.2(LIFR):c.756dup (p.Lys253Ter)

Gene:

LIFR:LIF receptor subunit alpha [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

5p13.1

Genomic location:

Preferred name:

NM_001127671.2(LIFR):c.756dup (p.Lys253Ter)

HGVS:

NC_000005.10:g.38510699dup
NG_011817.1:g.89707dup
NM_001127671.2:c.756dupMANE SELECT
NM_001364297.2:c.756dup
NM_001364298.2:c.756dup
NM_002310.6:c.756dup
NP_001121143.1:p.Lys253Ter
NP_001351226.1:p.Lys253Ter
NP_001351227.1:p.Lys253Ter
NP_002301.1:p.Lys253Ter
NC_000005.9:g.38510800_38510801insA
NC_000005.9:g.38510801dup
NM_001127671.1:c.756dup
NM_002310.5:c.756dup
NM_002310.5:c.756dupT

Protein change:

K253*

Links:

dbSNP: rs1745753552

NCBI 1000 Genomes Browser:

rs1745753552

Molecular consequence:

NM_001127671.2:c.756dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001364297.2:c.756dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001364298.2:c.756dup - nonsense - [Sequence Ontology: SO:0001587]
NM_002310.6:c.756dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Stuve-Wiedemann syndrome
Synonyms:: Schwartz-Jampel syndrome type 2; Schwartz-Jampel syndrome neonatal; Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0031280; MedGen: C0796176; Orphanet: 3206; OMIM: PS601559

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002059481	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 19, 2019)	biparental	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002103032	Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 10, 2021)	biparental	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003922864	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24477277, 19371797, 14740318 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002059481

Centogene AG - the Rare Disease Company

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 19, 2019)

biparental

clinical testing

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

SCV002103032

Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 10, 2021)

biparental

clinical testing

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

SCV003922864

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Mar 17, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	biparental	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Long-term follow-up in Stuve-Wiedemann syndrome: a case report with articular involvement.

Buonuomo PS, Macchiaiolo M, Cambiaso P, Rana I, Digilio MC, Bartuli A.

Clin Dysmorphol. 2014 Apr;23(2):45-46. doi: 10.1097/MCD.0000000000000023. No abstract available.

PubMed [citation]

PMID:: 24477277

See all PubMed Citations (4)

Details of each submission

From Centogene AG - the Rare Disease Company, SCV002059481.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	biparental	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn, SCV002103032.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

PVS1, PS4_moderate, PM2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	biparental	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003922864.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: LIFR c.756dupT (p.Lys253X), also referred to as c.756_757insT, results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250744 control chromosomes (gnomAD). c.756dupT has been reported in the literature in multiple homozygous individuals affected with Stuve-Wiedemann Syndrome (e.g. Dangoneau_2004, Corona-Rivera_2009, Buonuomo_2014). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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