ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.2292G>T (p.Gly764=) (rs142352887)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000429125 SCV000513594 uncertain significance not provided 2017-09-11 criteria provided, single submitter clinical testing The c.2292 G>T variant in the MEFV gene has been reported previously in one individual withfamilial Mediterranean fever (Jeske et al., 2013). This variant was not observed at any significantfrequency in approximately 6500 individuals of European and African American ancestry in theNHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In-silico splice prediction models predict that c.2292 G>T may create a cryptic splice donor site inexon 10 that could supplant the natural splice donor site. However, in the absence of RNA/functionalstudies, the actual effect of c.2292 G>T in this individual is unknown. We interpret c.2292 G>T as avariant of uncertain significance.
Invitae RCV000989470 SCV001097721 likely benign Familial Mediterranean fever 2020-11-26 criteria provided, single submitter clinical testing
Mendelics RCV000989470 SCV001139806 uncertain significance Familial Mediterranean fever 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000190 SCV001156687 uncertain significance not specified 2019-06-05 criteria provided, single submitter clinical testing The MEFV c.2292G>T; p.Gly764Gly variant (rs142352887) is reported in the medical literature in an individual with a clinical diagnosis of FMF (Jeske 2013). However, the variant has also been described as likely benign by a group of experts (Van Gijn 2018). The variant is described in the ClinVar database (Variation ID: 378133) and in the general population with an allele frequency of 0.02% (63/282832 alleles) in the Genome Aggregation Database. This is a synonymous variant in a weakly conserved nucleotide but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor splice site, removing a portion of the pyrin domain. Due to conflicting information, the clinical significance of the variant is uncertain at this time. References: Jeske M et al. Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study. Klin Padiatr. 2013 Nov;225(6):325-30. Van Gijn ME et al. New workflow for classification of genetic variants' pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). J Med Genet. 2018 Aug;55(8):530-537.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000429125 SCV001501589 likely benign not provided 2020-08-01 criteria provided, single submitter clinical testing
Natera, Inc. RCV000989470 SCV001458293 likely benign Familial Mediterranean fever 2020-01-09 no assertion criteria provided clinical testing

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