ClinVar Miner

Submissions for variant NM_001378615.1(CC2D2A):c.3341C>T (p.Thr1114Met)

gnomAD frequency: 0.00003  dbSNP: rs386833752
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program, University of Washington RCV000201581 SCV000256360 pathogenic Joubert syndrome 9 2015-02-23 criteria provided, single submitter research
GeneDx RCV001539860 SCV001757680 likely pathogenic not provided 2024-06-03 criteria provided, single submitter clinical testing Reported in a patient with Meckel syndrome who also harbored a second CC2D2A variant (PMID: 19466712); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19777577, 38036193, 26092869, 34234304, 31964843, 19466712)
Labcorp Genetics (formerly Invitae), Labcorp RCV002514252 SCV003287032 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1114 of the CC2D2A protein (p.Thr1114Met). This variant is present in population databases (rs386833752, gnomAD 0.01%). This missense change has been observed in individual(s) with CC2D2A-related conditions (PMID: 19466712, 19777577, 26092869). 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: 56304). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CC2D2A protein function. For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049716 SCV000082123 probable-pathogenic Meckel syndrome, type 6 no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Genomic Medicine Lab, University of California San Francisco RCV001007916 SCV001167625 uncertain significance Polydactyly 2018-07-26 flagged submission clinical testing

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