Submissions for variant NM_000975.5(RPL11):c.311del (p.Asn104fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003616627	SCV004504775	pathogenic	Diamond-Blackfan anemia	2023-02-21	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the RPL11 gene (p.Asn104Thrfs*90). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 75 amino acid(s) of the RPL11 protein and extend the protein by 14 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RPL11-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the RPL11 protein in which other variant(s) (p.His155Glnfs*16) have been determined to be pathogenic (PMID: 19773262; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.