ClinVar Miner

Submissions for variant NM_001080522.2(CC2D2A):c.4582C>T (p.Arg1528Cys) (rs118204052)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program,University of Washington RCV000000780 SCV000256335 pathogenic Joubert syndrome 9 2015-02-23 criteria provided, single submitter research
GeneDx RCV000445290 SCV000520848 likely pathogenic not provided 2018-03-29 criteria provided, single submitter clinical testing A likely pathogenic variant has been identified in the CC2D2A gene. The R1528C variant has been reported previously in trans with the c.3774dupT variant in an individual with JSRD (Bachmann-Gagescu et al., 2015). Additionally, R1528C has been observed in trans with other CC2D2A variants (c.3289delG; c.3772-1G>T) and in the homozygous state in association with COACH syndrome and JSRD (Bachmann-Gagescu et al., 2015; Gorden et al., 2008). Different missense variants at the same codon (R1528H) and in a nearby residue (T1526N) have also been reported in the Human Gene Mutation Database in association with Joubert syndrome (Ben-Salem et al., 2014; Stenson et al., 2014). The R1528C variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species; however, the R1528C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, the R1528C variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
OMIM RCV000000780 SCV000020930 pathogenic Joubert syndrome 9 2008-11-01 no assertion criteria provided literature only

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