ClinVar Miner

Submissions for variant NM_001080522.2(CC2D2A):c.4465_4468del (p.Asp1489fs) (rs797045437)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193046 SCV000246903 pathogenic Joubert syndrome 9 2015-04-23 criteria provided, single submitter clinical testing
GeneDx RCV000627446 SCV000748446 likely pathogenic not provided 2018-03-09 criteria provided, single submitter clinical testing The c.4465_4468delGACA variant in the CC2D2A gene has been reported previously, along with another variant, in an individual with nephronophthisis and Meckel-Gruber syndrome (Schueler et al., 2016). The c.4465_4468delGACA variant causes a frameshift starting with codon Asparagine 1489, changes this amino acid to a Lysine residue, and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Asp1489LysfsX15. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.4465_4468delGACA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.4465_4468delGACA as a variant of uncertain significance.
Invitae RCV000687812 SCV000815400 pathogenic Joubert syndrome; Meckel-Gruber syndrome 2017-09-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp1489Lysfs*15) in the CC2D2A 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 on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with nephronophthisis and Meckel-Gruber syndrome (PMID: 26673778). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 210612). Loss-of-function variants in CC2D2A are known to be pathogenic (PMID: 19777577). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000627446 SCV000855497 pathogenic not provided 2017-07-11 criteria provided, single submitter clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000627446 SCV000778198 pathogenic not provided 2016-05-24 no assertion criteria provided clinical testing

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