Submissions for variant NM_000975.5(RPL11):c.465_466del (p.His155fs)

dbSNP: rs1644530053

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002339708	SCV002636813	likely pathogenic	Diamond-Blackfan anemia	2014-12-11	criteria provided, single submitter	clinical testing	The c.465_466delCA variant, located in coding exon 5 of the RPL11 gene, results from a deletion of two nucleotides between positions 465 and 466, causing a translational frameshift with a predicted alternate stop codon (p.H155Qfs*16). This alteration was reported as a de novo mutation in a 10 year old female diagnosed with Diamond-Blackfan anemia; her clinical features included a septal atrial defect, flat thenar eminence, short stature, no response to steroids and she was transfusion dependent (Quarello P et al. Haematologica. 2010; 95:206-13). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. This nucleotide region is conserved through reptiles. Per ACMG guidelines this variant could be interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294); however, this deletion and subsequent frameshift occur at the 3' terminus of RPL11 and result in the removal of only the last 9 amino acids of the protein. The exact functional impact of these deleted amino acids is unknown at this time. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002339708	SCV003523262	likely pathogenic	Diamond-Blackfan anemia	2023-09-06	criteria provided, single submitter	clinical testing	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: 992969). This premature translational stop signal has been observed in individual(s) with clinical features of Diamond-Blackfan anemia (PMID: 19773262; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His155Glnfs*16) in the RPL11 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the RPL11 protein.
Revvity Omics, Revvity	RCV001283765	SCV003824964	pathogenic	Diamond-Blackfan anemia 7	2022-11-21	criteria provided, single submitter	clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV001283765	SCV001469134	pathogenic	Diamond-Blackfan anemia 7	2020-08-07	no assertion criteria provided	clinical testing