Submissions for variant NM_000975.5(RPL11):c.465_475dup (p.Lys159fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002330453	SCV002634265	likely pathogenic	Diamond-Blackfan anemia	2017-10-30	criteria provided, single submitter	clinical testing	The c.465_475dup11 variant, located in coding exon 5 of the RPL11 gene, results from a duplication of CAGAATCAGCA at nucleotide position 465, causing a translational frameshift with a predicted alternate stop codon (p.K159Tfs*39). Several similar frameshift alterations (c.462delA, c.465_466delCA, c.469delA, c.476_477delAA, c.482_484delAGG, c.489_490delGCinsT) have been identified in individuals with Diamond-Blackfan anemia, including three that impact residues downstream of amino acid position 159 (Gazda HT et al. Am. J. Hum. Genet. 2008 Dec;83(6):769-80; Quarello P et al. Haematologica. 2010 Feb;95(2):206-13; Gerrard G et al. Haematologica. 2013 Aug;162(4):530-6; Fores Ballester E et al. Clin Case Rep. 2015 Jun;3(6):392-5). Frameshifts are typically deleterious in nature; however, this frameshift occurs at the 3' terminus of RPL11, is not expected to trigger nonsense-mediated mRNA decay, and results in the elongation of the protein by 17 amino acids. The exact functional impact of these inserted amino acids is unknown at this time. Based on the majority of available evidence to date, this variant is likely to be pathogenic.