ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.2837G>A (p.Arg946Gln) (rs149824485)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236700 SCV000294162 uncertain significance not provided 2017-10-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the IGHMBP2 gene. The R946Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R946Q variant is observed in 159/126,180 (0.1%) alleles from individuals of European background (Lek et al., 2016). The R946Q variant is a semi-conservative amino acidsubstitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000292250 SCV000373811 uncertain significance Spinal muscular atrophy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000556244 SCV000642353 uncertain significance Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2018-11-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 946 of the IGHMBP2 protein (p.Arg946Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs149824485, ExAC 0.1%). This variant has not been reported in the literature in individuals with IGHMBP2-related disease. ClinVar contains an entry for this variant (Variation ID: 246570). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Athena Diagnostics Inc RCV000236700 SCV001144479 likely benign not provided 2019-02-27 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000236700 SCV001148364 uncertain significance not provided 2019-05-01 criteria provided, single submitter clinical testing

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