ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.2932G>C (p.Ala978Pro)

gnomAD frequency: 0.00002  dbSNP: rs368905339
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000810357 SCV000950553 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2022-05-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 978 of the PLEKHG5 protein (p.Ala978Pro). This variant is present in population databases (rs368905339, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 654396). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002440744 SCV002748581 uncertain significance Inborn genetic diseases 2019-12-27 criteria provided, single submitter clinical testing The p.A978P variant (also known as c.2932G>C), located in coding exon 19 of the PLEKHG5 gene, results from a G to C substitution at nucleotide position 2932. The alanine at codon 978 is replaced by proline, an amino acid with highly similar properties. This amino acid position is not well 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.

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