Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519412 | SCV000621540 | uncertain significance | not provided | 2017-10-10 | criteria provided, single submitter | clinical testing | The c.203-3 T>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.203-3 T>G variant is observed in 50/29132 (0.2%) alleles from individuals of Latino background (Lek et al., 2016). This variant is predicted to damage or destroy the splice acceptor site in intron 2, and is expected to cause abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Additionally, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Labcorp Genetics |
RCV000519412 | SCV002294653 | uncertain significance | not provided | 2021-12-07 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the LARP7 gene. It does not directly change the encoded amino acid sequence of the LARP7 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs201651306, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with LARP7-related conditions. ClinVar contains an entry for this variant (Variation ID: 452711). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. |
Prevention |
RCV003960239 | SCV004779451 | likely benign | LARP7-related disorder | 2021-06-08 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |