ClinVar Miner

Submissions for variant NM_001378183.1(PIEZO2):c.4775_4778del (p.Lys1592fs)

dbSNP: rs2510489205
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV003142513 SCV003807033 likely pathogenic Arthrogryposis, distal, with impaired proprioception and touch 2022-07-21 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PM2 moderated
Illumina Laboratory Services, Illumina RCV003142513 SCV004014683 pathogenic Arthrogryposis, distal, with impaired proprioception and touch 2023-02-03 criteria provided, single submitter clinical testing The PIEZO2 c.4700_4703del (p.Lys1567ArgfsTer82) variant results in the deletion of four nucleotides at position c.4700_4703, causing a shift in the protein reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. To our knowledge, this variant has not been reported in the peer-reviewed literature. The variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. This variant was identified in a homozygous state. Based on the available evidence, the c.4700_4703del (p.Lys1567ArgfsTer82) variant is classified as pathogenic for distal arthrogryposis with impaired proprioception and touch.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003492822 SCV004241954 pathogenic FAM38B-related disorder 2023-12-07 criteria provided, single submitter clinical testing Variant summary: FAM38B(PIEZO2) c.4700_4703delAGAA (p.Lys1567ArgfsX82) results in a premature termination codon and is expected to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant was absent in 141916 control chromosomes (gnomAD). To our knowledge, no occurrence of c.4700_4703delAGAA in individuals affected with FAM38B-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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