ClinVar Miner

Submissions for variant NM_002180.3(IGHMBP2):c.2960G>A (p.Arg987Gln)

gnomAD frequency: 0.00009  dbSNP: rs199863781
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001869314 SCV002213820 likely benign Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S 2024-02-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002434054 SCV002752050 uncertain significance Inborn genetic diseases 2022-07-20 criteria provided, single submitter clinical testing The p.R987Q variant (also known as c.2960G>A), located in coding exon 15 of the IGHMBP2 gene, results from a G to A substitution at nucleotide position 2960. The arginine at codon 987 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been detected in the heterozygous state in an individual with limb-girdle-muscular dystrophy (Yu M et al. PLoS One, 2017 Apr;12:e0175343). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004768718 SCV005381150 uncertain significance not specified 2024-08-13 criteria provided, single submitter clinical testing Variant summary: IGHMBP2 c.2960G>A (p.Arg987Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.6e-05 in 242258 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in IGHMBP2 causing Charcot-Marie-Tooth Disease, Axonal, Type 2S, allowing no conclusion about variant significance. c.2960G>A has been reported in the literature in a compound heterozygous individuals affected with Charcot-Marie-Tooth Disease, Axonal, Type 2S with an unknown second allele variant (Yu_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Charcot-Marie-Tooth Disease, Axonal, Type 2S. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 28403181). ClinVar contains an entry for this variant (Variation ID: 694864). Based on the evidence outlined above, the variant was classified as uncertain significance.
Genesis Genome Database RCV000856984 SCV000999552 uncertain significance Neuronopathy, distal hereditary motor, autosomal dominant 2019-08-14 no assertion criteria provided research

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