ClinVar Miner

Submissions for variant NM_001005361.3(DNM2):c.869G>A (p.Arg290Gln)

gnomAD frequency: 0.00004  dbSNP: rs117398902
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kariminejad - Najmabadi Pathology & Genetics Center RCV001007469 SCV001167084 uncertain significance Charcot-Marie-Tooth disease dominant intermediate B criteria provided, single submitter clinical testing
Invitae RCV001007469 SCV001230660 uncertain significance Charcot-Marie-Tooth disease dominant intermediate B 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 290 of the DNM2 protein (p.Arg290Gln). This variant is present in population databases (rs117398902, gnomAD 0.006%). This missense change has been observed in individuals with Charcot-Marie-Tooth disease and/or congenital myopathy (PMID: 32657593, 33333461). ClinVar contains an entry for this variant (Variation ID: 816534). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNM2 protein function. 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.
Ambry Genetics RCV002372730 SCV002685223 uncertain significance Inborn genetic diseases 2021-04-08 criteria provided, single submitter clinical testing The p.R290Q variant (also known as c.869G>A), located in coding exon 7 of the DNM2 gene, results from a G to A substitution at nucleotide position 869. The arginine at codon 290 is replaced by glutamine, an amino acid with highly similar properties. This variant was detected in an individual with congenital myopathy (Natera-de Benito D et al. Pediatr Neurol, 2021 Feb;115:50-65). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003106093 SCV003761766 uncertain significance not provided 2022-07-28 criteria provided, single submitter clinical testing Identified in a patient with congenital myopathy, but it is unknown whether this individual was tested for variants in other genes associated with congenital myopathy (Natera-de Benito et al., 2021); Reported in a patient with hereditary neuropathy; however, familial segregation information was not included (Taghizadeh et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 16227997, 33333461, 32657593)

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