ClinVar Miner

Submissions for variant NM_182943.3(PLOD2):c.1559dup (p.Val523fs)

dbSNP: rs749709000
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003556107 SCV004293523 pathogenic not provided 2023-05-09 criteria provided, single submitter clinical testing This variant is present in population databases (rs749709000, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Val523Cysfs*7) in the PLOD2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PLOD2 are known to be pathogenic (PMID: 22689593, 25238597, 29178448). This premature translational stop signal has been observed in individual(s) with Bruck syndrome (PMID: 22689593, 35278031). ClinVar contains an entry for this variant (Variation ID: 41424). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004799755 SCV005422318 pathogenic Osteogenesis imperfecta 2024-10-14 criteria provided, single submitter clinical testing Variant summary: PLOD2 c.1559dupC (p.Val523CysfsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 248858 control chromosomes (gnomAD). c.1559dupC has been reported in the literature in individuals affected with PLOD2-related conditions (example: Otaify_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35278031). ClinVar contains an entry for this variant (Variation ID: 41424). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000034323 SCV000058274 pathogenic Bruck syndrome 2 2012-10-01 no assertion criteria provided literature only

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