ClinVar Miner

Submissions for variant NM_001283009.2(RTEL1):c.2413+1G>C

dbSNP: rs776744306
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University of Washington Center for Mendelian Genomics, University of Washington RCV000201651 SCV000256242 pathogenic Interstitial lung disease 2 2015-05-19 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590169 SCV000699747 likely pathogenic Dyskeratosis congenita 2016-06-16 criteria provided, single submitter clinical testing Variant summary: The RTEL1 c.2485+1G>C variant involves the alteration of a conserved GT donor splice site of intron 26. One in silico tool predicts a damaging outcome for this variant along with 5/5 splice tools predicting the variant to result in the elimination of the splice donor site at the exon 26 / intron 26 border. This variant is absent from 106922 control chromosomes and to our knowledge, was only reported in a family with idiopathic interstitial pneumonia with suspected AD mode of inheritance. One clinical diagnostic laboratory classified this variant as Pathogenic for Idiopathic fibrosing alveolitis, chronic form. Considering the impact of the variant on canonical splice site, it was classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003765296 SCV004571453 likely pathogenic Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2023-03-24 criteria provided, single submitter clinical testing 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 217284). Disruption of this splice site has been observed in individual(s) with familial interstitial pneumonia (FIP) (PMID: 25607374). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 26 of the RTEL1 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), and loss-of-function variants in RTEL1 are known to be pathogenic (PMID: 23453664, 23959892, 25607374).
OMIM RCV003329258 SCV000255955 pathogenic Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2015-03-15 no assertion criteria provided literature only

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