Submissions for variant NM_001283009.2(RTEL1):c.2783_2784del (p.Phe928fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003798376	SCV004581734	pathogenic	Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	2023-10-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe928Cysfs*13) in the RTEL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RTEL1 are known to be pathogenic (PMID: 23453664, 23959892, 25607374). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004736399	SCV005341789	likely pathogenic	RTEL1-related disorder	2024-03-05	no assertion criteria provided	clinical testing	The RTEL1 c.2855_2856delTC variant is predicted to result in a frameshift and premature protein termination (p.Phe952Cysfs*13). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. Frameshift variants in RTEL1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.