ClinVar Miner

Submissions for variant NM_001378615.1(CC2D2A):c.1017+1G>A

gnomAD frequency: 0.00008  dbSNP: rs200407856
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000198057 SCV000253860 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2024-11-05 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the CC2D2A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CC2D2A are known to be pathogenic (PMID: 19777577). This variant is present in population databases (rs200407856, gnomAD 0.04%). Disruption of this splice site has been observed in individual(s) with Joubert syndrome (PMID: 26092869; internal data). 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: 166801). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
UW Hindbrain Malformation Research Program, University of Washington RCV000201663 SCV000256347 pathogenic Joubert syndrome 9 2015-02-23 criteria provided, single submitter research
Eurofins Ntd Llc (ga) RCV000597652 SCV000700659 pathogenic not provided 2017-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000597652 SCV002006751 pathogenic not provided 2024-08-06 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29146704, 22848652, 28497568, 26092869, 22241855)
Fulgent Genetics, Fulgent Genetics RCV005031661 SCV005660516 likely pathogenic Meckel syndrome, type 6; Joubert syndrome 9; COACH syndrome 2; Retinitis pigmentosa 93 2024-04-09 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004732713 SCV005361330 likely pathogenic CC2D2A-related disorder 2024-04-30 no assertion criteria provided clinical testing The CC2D2A c.1017+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported along with a second CC2D2A variant in at least one individual with Joubert syndrome (Supplemental Table S5 in Bachmann-Gagescu et al. 2015. PubMed ID: 26092869). This variant is reported in 0.031% of alleles in individuals of African descent in gnomAD. Variants that disrupt the consensus splice donor site in CC2D2A are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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