NM_001127671.2(LIFR):c.3288C>A (p.Asn1096Lys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 11, 2024
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:: RCV003155170.2

Allele description [Variation Report for NM_001127671.2(LIFR):c.3288C>A (p.Asn1096Lys)]

NM_001127671.2(LIFR):c.3288C>A (p.Asn1096Lys)

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.3288C>A (p.Asn1096Lys)

HGVS:

NC_000005.10:g.38481601G>T
NG_011817.1:g.118805C>A
NM_001127671.2:c.3288C>AMANE SELECT
NM_001364297.2:c.3288C>A
NM_001364298.2:c.3255C>A
NM_002310.6:c.3288C>A
NP_001121143.1:p.Asn1096Lys
NP_001351226.1:p.Asn1096Lys
NP_001351227.1:p.Asn1085Lys
NP_002301.1:p.Asn1096Lys
NC_000005.9:g.38481703G>T
NM_002310.5:c.3288C>A

Protein change:

N1085K

Links:

dbSNP: rs3729751

NCBI 1000 Genomes Browser:

rs3729751

Molecular consequence:

NM_001127671.2:c.3288C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001364297.2:c.3288C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001364298.2:c.3255C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002310.6:c.3288C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003844901	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jan 11, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34426522, 26627873, 34063511, 28334964 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003844901

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jan 11, 2024)

germline

clinical testing

PubMed (4)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The genetic structure of the Turkish population reveals high levels of variation and admixture.

Kars ME, Başak AN, Onat OE, Bilguvar K, Choi J, Itan Y, Çağlar C, Palvadeau R, Casanova JL, Cooper DN, Stenson PD, Yavuz A, Buluş H, Günel M, Friedman JM, Özçelik T.

Proc Natl Acad Sci U S A. 2021 Sep 7;118(36). doi:pii: e2026076118. 10.1073/pnas.2026076118. Erratum in: Proc Natl Acad Sci U S A. 2021 Dec 28;118(52):.

PubMed [citation]

PMID:: 34426522
PMCID:: PMC8433500

Targeted next-generation sequencing assay for detection of mutations in primary myopathies.

Evilä A, Arumilli M, Udd B, Hackman P.

Neuromuscul Disord. 2016 Jan;26(1):7-15. doi: 10.1016/j.nmd.2015.10.003. Epub 2015 Nov 25.

PubMed [citation]

PMID:: 26627873

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844901.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: LIFR c.3288C>A (p.Asn1096Lys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 250856 control chromosomes. The observed variant frequency is approximately 1.34 fold of the estimated maximal expected allele frequency for a pathogenic variant in LIFR causing Stuve-Wiedemann Syndrome phenotype (0.0011), suggesting that the variant may be benign. c.3288C>A has been reported in the literature in individuals affected with congenital anomalies of the kidneys and urinary tract (Kosfeld_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Stuve-Wiedemann Syndrome. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in >50%-90% of normal activity (Kosfeld_2017). ClinVar contains an entry for this variant (Variation ID: 353605). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

#	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: Apr 15, 2024

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