ClinVar Miner

Submissions for variant NM_001080522.2(CC2D2A):c.3289delG (rs386833751)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program,University of Washington RCV000201550 SCV000256334 pathogenic Joubert syndrome 9 2015-02-23 criteria provided, single submitter research
Genetic Services Laboratory,University of Chicago RCV000201550 SCV000593889 pathogenic Joubert syndrome 9 2016-05-17 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727050 SCV000705167 pathogenic not provided 2016-12-29 criteria provided, single submitter clinical testing
Invitae RCV000817119 SCV000957664 pathogenic Joubert syndrome; Meckel-Gruber syndrome 2019-10-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1097Phefs*2) in the CC2D2A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs770470219, ExAC 0.07%). This variant has been observed in combination with another CC2D2A variant in individuals affected with Joubert syndrome (PMID: 18950740, 22241855) and Meckel syndrome (PMID: 19466712). ClinVar contains an entry for this variant (Variation ID: 56303). Loss-of-function variants in CC2D2A are known to be pathogenic (PMID: 19777577). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000727050 SCV001168531 pathogenic not provided 2018-07-12 criteria provided, single submitter clinical testing The c.3289delG variant in the CC2D2A gene was identified in a patient with COACH syndrome who harbored a second variant on the opposite allele, and was also detected in two siblings with Joubert syndrome who did not have a second identifiable variant (Gorden et al., 2008). This variant has also been reported in trans with another CC2D2A variant in a family with Meckel syndrome (Tallila et al., 2009). The c.3289delG variant causes a frameshift starting with codon Valine 1097, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 2 of the new reading frame, denoted p.V1097FfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3289delG variant is observed in 50/118648 (0.04%) alleles from individuals of European (Non-Finnish) background, in large population cohorts and no individuals were reported to be homozygous (Lek et al., 2016). We interpret c.3289delG as a pathogenic variant.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000727050 SCV001249102 pathogenic not provided 2020-06-01 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049715 SCV000082122 probable-pathogenic Meckel syndrome type 6 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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