ClinVar Miner

Submissions for variant NM_001005498.4(RHBDF2):c.2365G>A (p.Ala789Thr)

gnomAD frequency: 0.00006  dbSNP: rs770206566
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000352768 SCV000406840 benign Palmoplantar keratoderma-esophageal carcinoma 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 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.
Baylor Genetics RCV000352768 SCV001481436 uncertain significance Palmoplantar keratoderma-esophageal carcinoma syndrome 2019-03-19 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV003546528 SCV004270652 uncertain significance not provided 2023-01-17 criteria provided, single submitter clinical testing This variant is present in population databases (rs770206566, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 818 of the RHBDF2 protein (p.Ala818Thr). This variant has not been reported in the literature in individuals affected with RHBDF2-related conditions. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 325421).

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