ClinVar Miner

Submissions for variant NM_020631.5(PLEKHG5):c.2053C>T (p.Gln685Ter) (rs772217003)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579101 SCV000680998 pathogenic not provided 2017-07-10 criteria provided, single submitter clinical testing The Q685X nonsense variant in the PLEKHG5 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q685X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although this pathogenic variant has not been reported previously to our knowledge, we interpret Q685X as a pathogenic variant, and homozygosity for this variant is consistent with the diagnosis of a PLEKHG5-related neuropathy in this individual. However, this result could also be seen if the patient had one allele with the Q685X pathogenic variant and another allele that was partially missing or refractory to amplification.
Invitae RCV000807298 SCV000947345 pathogenic Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c 2018-08-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln685*) in the PLEKHG5 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs772217003, ExAC 0.02%). This variant has not been reported in the literature in individuals with PLEKHG5-related disease. ClinVar contains an entry for this variant (Variation ID: 489025). Loss-of-function variants in PLEKHG5 are known to be pathogenic (PMID: 17564964, 23777631). For these reasons, this variant has been classified as Pathogenic.

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