Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493304 | SCV000582260 | likely pathogenic | not provided | 2017-05-12 | criteria provided, single submitter | clinical testing | The c.762+1G>A variant in the COMP gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site of intron 7, and is predicted to cause abnormal gene splicing resulting in an in-frame protein product with an abnormal message. The c.762+1G>A variant is observed in 1/6162 (0.02%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). We interpret c.762+1G>A as a likely pathogenic variant. |
Invitae | RCV000493304 | SCV004467153 | uncertain significance | not provided | 2023-08-27 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 7 of the COMP gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in COMP cause disease. This variant is present in population databases (rs755374221, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with COMP-related conditions. ClinVar contains an entry for this variant (Variation ID: 429642). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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. |