Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002516543 | SCV003297817 | uncertain significance | Dyskeratosis congenita, autosomal recessive 6; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 9 of the PARN gene. It does not directly change the encoded amino acid sequence of the PARN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs759131762, gnomAD 0.01%). This variant has been observed in individual(s) with bone marrow failure (PMID: 25893599). ClinVar contains an entry for this variant (Variation ID: 190291). 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. |
| Gene |
RCV003327376 | SCV004034662 | uncertain significance | not provided | 2023-03-09 | criteria provided, single submitter | clinical testing | Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 17576681, 9536098, 25893599) |
| OMIM | RCV000170487 | SCV000222914 | pathogenic | Dyskeratosis congenita, autosomal recessive 6 | 2015-05-01 | no assertion criteria provided | literature only |