ClinVar Miner

Submissions for variant NM_001127671.2(LIFR):c.1937C>A (p.Thr646Asn)

gnomAD frequency: 0.00875  dbSNP: rs79040751
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224818 SCV000281205 likely benign not provided 2015-06-12 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003761833 SCV000604099 benign Stüve-Wiedemann syndrome 1 2023-11-29 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000505869 SCV000862038 benign not specified 2018-06-29 criteria provided, single submitter clinical testing
Invitae RCV000224818 SCV001103028 benign not provided 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000999980 SCV001318857 benign Stuve-Wiedemann syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV000224818 SCV001868939 benign not provided 2019-05-28 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28334964)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277581 SCV002566888 benign Connective tissue disorder 2022-02-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000505869 SCV003844624 benign not specified 2023-02-13 criteria provided, single submitter clinical testing Variant summary: LIFR c.1937C>A (p.Thr646Asn) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0021 in 251466 control chromosomes, predominantly at a frequency of 0.026 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 23 fold of the estimated maximal expected allele frequency for a pathogenic variant in LIFR causing Stuve-Wiedemann Syndrome phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1937C>A in individuals affected with Stuve-Wiedemann Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely pathogenic n=1, benign/likely benign n=8). Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences RCV003919908 SCV004735750 likely benign LIFR-related condition 2019-06-04 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Weber Lab, Hannover Medical School RCV000491876 SCV000346033 uncertain significance Congenital anomaly of kidney and urinary tract 2024-02-15 no assertion criteria provided research
Natera, Inc. RCV000999980 SCV002084261 benign Stuve-Wiedemann syndrome 2019-11-15 no assertion criteria provided clinical testing

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