ClinVar Miner

Submissions for variant NM_207111.4(RNF216):c.2374G>A (p.Asp792Asn)

dbSNP: rs1012568298
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001906203 SCV002177179 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 792 of the RNF216 protein (p.Asp792Asn). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1397588). This missense change has been observed in individual(s) with congenital hypogonadotropic hypogonadism (PMID: 32982993). This variant is not present in population databases (gnomAD no frequency).
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002471183 SCV002768715 uncertain significance Cerebellar ataxia-hypogonadism syndrome 2019-08-28 criteria provided, single submitter clinical testing A heterozygous missense variant was identified, NM_207111.3(RNF216):c.2374G>A in exon 15 of 17 of the RNF216 gene. This substitution is predicted to create a minor amino acid change from aspartic acid to asparagine at position 792 of the protein, NP_996994.1(RNF216):p.(Asp792Asn). The aspartic acid at this position has very high conservation (100 vertebrates, UCSC), but is not situated in a domain. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database, and has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).

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