ClinVar Miner

Submissions for variant NM_000969.5(RPL5):c.67C>T (p.Arg23Ter)

dbSNP: rs121434405
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627210 SCV000748197 pathogenic not provided 2023-05-15 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23744582, 25525159, 28991257, 32368696, 33084842, 19061985)
Labcorp Genetics (formerly Invitae), Labcorp RCV001217229 SCV001389063 pathogenic Diamond-Blackfan anemia 2019-04-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg23*) in the RPL5 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Diamond-Blackfan anemia (PMID: 19061985) and an individual with congenital heart disease (PMID: 28991257). ClinVar contains an entry for this variant (Variation ID: 6179). Loss-of-function variants in RPL5 are known to be pathogenic (PMID: 19061985, 19773262). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001217229 SCV002661839 pathogenic Diamond-Blackfan anemia 2020-09-14 criteria provided, single submitter clinical testing The p.R23* pathogenic mutation (also known as c.67C>T), located in coding exon 2 of the RPL5 gene, results from a C to T substitution at nucleotide position 67. This changes the amino acid from an arginine to a stop codon within coding exon 2. This alteration was reported to occur de novo in an individual diagnosed with Diamond-Blackfan anemia (DBA) who was also born with cleft lip and palate (Gazda HT et al. Am. J. Hum. Genet., 2008 Dec;83:769-80), and has been detected in other DBA cohorts and in a congenital heart disease cohort (Smetanina NS et al. Pediatr Blood Cancer. 2015 Sep;62(9):1597-600; Jin SC et al. Nat. Genet. 2017 Nov;49(11):1593-1601). A study of induced pluripotent stem cells derived from a patient with this mutation reported defects in ribosome biogenesis and hematopoiesis (Garçon L et al. Blood. 2013 Aug;122(6):912-21). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
OMIM RCV000006556 SCV000026739 pathogenic Diamond-Blackfan anemia 6 2008-12-01 no assertion criteria provided literature only

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