Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000501430 | SCV000596812 | uncertain significance | not specified | 2017-01-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000651123 | SCV000772973 | likely benign | Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 | 2024-01-11 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000501430 | SCV004222790 | likely benign | not specified | 2023-11-16 | criteria provided, single submitter | clinical testing | Variant summary: RTEL1 c.1421-9G>A alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.2e-05 in 237398 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in RTEL1 causing Dyskeratosis Congenita (Hoyeraal Hreidarsson Syndrome) (4.2e-05 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1421-9G>A in individuals affected with Dyskeratosis Congenita (Hoyeraal Hreidarsson Syndrome) and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have reported this variant to ClinVar after 2014 with conflicting assessments (likely benign, n = 2; uncertain significance, n = 1). Based on the evidence outlined above, the variant was classified as likely benign. |
Natera, |
RCV001275092 | SCV001459846 | likely benign | Dyskeratosis congenita, autosomal dominant 1 | 2020-06-13 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004541568 | SCV004767815 | likely benign | RTEL1-related disorder | 2020-10-23 | no assertion criteria provided | 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). |