ClinVar Miner

Submissions for variant NM_000969.5(RPL5):c.169_172del (p.Asn57fs) (rs1558284033)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000702906 SCV000831781 pathogenic Diamond-Blackfan anemia 2019-03-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn57Glufs*12) 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 reported in individuals with Diamond-Blackfan anemia (PMID: 19061985, 23718193, 19773262, 20960466) including one de novo observation (PMID: 19773262). This variant is also known as 166_169del (56_57del) in the literature. Loss-of-function variants in RPL5 are known to be pathogenic (PMID: 19773262, 19061985). For these reasons, this variant has been classified as Pathogenic.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000761557 SCV000889935 pathogenic Diamond-Blackfan anemia 1 2019-03-13 criteria provided, single submitter clinical testing The p.N57Qfs*12 variant in the RPL5 gene is a de novo frameshift variant, which is absent in the gnomAD database and has previously been reported as a pathogenic variant in the ClinVar database (Accession: RCV000702906.1). In summary, the p.N57Qfs*12 variant meets the ACMG criteria to be classified as pathogenic based upon inheritance model, absence from controls and previous ClinVar submission.
GeneDx RCV001008074 SCV001167812 pathogenic not provided 2019-02-04 criteria provided, single submitter clinical testing The c.169_172delAACA variant has been reported previously in association with Diamond-Blackfan anemia, including an apparently de novo occurrence (Cmejla et al., 2009; Quarello et al., 2010; Gerrard et al., 2013). The deletion causes a frameshift starting with codon Asparagine 57, changes this amino acid to a Glutamic acid residue and creates a premature Stop codon at position 12 of the new reading frame, denoted p.Asn57GlufsX12. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider the variant to be pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001008074 SCV001245631 pathogenic not provided 2018-06-01 criteria provided, single submitter clinical testing

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