ClinVar Miner

Submissions for variant NM_001127671.2(LIFR):c.3221A>G (p.Asp1074Gly) (rs147058538)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756307 SCV000884076 uncertain significance not provided 2018-05-03 criteria provided, single submitter clinical testing The LIFR: p.Asp1074Gly variant (rs147058538) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.02 percent (identified on 50 out of 277,068 chromosomes). This is a missense variant in a moderately conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor site weakening nearby interaction with exonic splicing enhancers. The aspartic acid at position 1074 is highly conserved up to frog considering 12 species and computational analyses of the effects of the p.Asp1074Gly variant on protein structure and function provide conflicting results (SIFT: tolerated, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Asp1074Gly variant with certainty.
Illumina Clinical Services Laboratory,Illumina RCV001151740 SCV001312905 uncertain significance Stüve-Wiedemann syndrome 2018-01-12 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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