ClinVar Miner

Submissions for variant NM_138477.4(CDAN1):c.156C>G (p.Phe52Leu)

gnomAD frequency: 0.00009  dbSNP: rs80338694
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483236 SCV000571213 likely pathogenic not provided 2017-07-25 criteria provided, single submitter clinical testing The F52L variant in the CDAN1 gene has been reported previously in association with congenital dyserythropoietic anemia in affected individuals who were heterozygous for the F52L variant and another CDAN1 variant; however, parental testing information was not provided to determine if the variants were in trans (Tamary et al., 2005; Roy et al., 2016). The F52L variant was not observed in approximately 5,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, though the average read depth at this position was low (5X). The F52L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The F52L variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Centogene AG - the Rare Disease Company RCV001807737 SCV002059789 likely pathogenic Anemia, congenital dyserythropoietic, type 1a 2019-05-21 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV001807737 SCV002761781 likely pathogenic Anemia, congenital dyserythropoietic, type 1a 2022-06-06 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000483236 SCV002817247 likely pathogenic not provided 2021-11-30 criteria provided, single submitter clinical testing This variant segregates with disease in at least one family (PMID: 33401150, 16098079, 27432187). The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). Computational tools yielded predictions that this amino acid change may be damaging to the protein. This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study.
Revvity Omics, Revvity RCV001807737 SCV003820562 likely pathogenic Anemia, congenital dyserythropoietic, type 1a 2023-10-16 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000483236 SCV004224617 likely pathogenic not provided 2023-02-20 criteria provided, single submitter clinical testing PP4, PP5, PM1, PM2, PM3
Invitae RCV000483236 SCV004296942 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 52 of the CDAN1 protein (p.Phe52Leu). This variant is present in population databases (rs80338694, gnomAD 0.02%). This missense change has been observed in individual(s) with autosomal recessive dyserythropoietic anemia (PMID: 27432187; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 21746). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. For these reasons, this variant has been classified as Pathogenic.

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