ClinVar Miner

Submissions for variant NM_015713.5(RRM2B):c.544A>G (p.Thr182Ala)

gnomAD frequency: 0.00005  dbSNP: rs147315735
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199003 SCV000252192 likely benign not specified 2014-03-19 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina RCV001164963 SCV001327126 likely benign Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina RCV001164964 SCV001327127 uncertain significance Mitochondrial DNA depletion syndrome 8a 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002517256 SCV002970244 uncertain significance not provided 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 182 of the RRM2B protein (p.Thr182Ala). This variant is present in population databases (rs147315735, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with RRM2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 215088). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RRM2B protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV005031731 SCV005669613 uncertain significance Mitochondrial DNA depletion syndrome 8a; Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 2024-04-30 criteria provided, single submitter clinical testing

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