ClinVar Miner

Submissions for variant NM_001378615.1(CC2D2A):c.4407C>G (p.Ser1469Arg)

gnomAD frequency: 0.00003  dbSNP: rs587779732
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000114181 SCV000147733 likely pathogenic Meckel-Gruber syndrome 2013-10-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001854529 SCV002304268 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1469 of the CC2D2A protein (p.Ser1469Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of Joubert syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 126245). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CC2D2A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV004721263 SCV005326837 uncertain significance not provided 2023-12-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Reported previously in unaffected carriers; however, no further information was provided (PMID: 31964843); This variant is associated with the following publications: (PMID: 31589614, 31964843)
Mayo Clinic Laboratories, Mayo Clinic RCV004721263 SCV005410532 uncertain significance not provided 2023-06-26 criteria provided, single submitter clinical testing PM2_moderate

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