Submissions for variant NM_001080522.2(CC2D2A):c.4179+1del (rs386833760)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194003	SCV000246901	pathogenic	Joubert syndrome 9	2014-09-22	criteria provided, single submitter	clinical testing
UW Hindbrain Malformation Research Program,University of Washington	RCV000194003	SCV000256339	pathogenic	Joubert syndrome 9	2015-02-23	criteria provided, single submitter	research
Genetic Services Laboratory, University of Chicago	RCV000049724	SCV000593890	pathogenic	Meckel syndrome type 6	2014-09-04	criteria provided, single submitter	clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000725911	SCV000701189	pathogenic	not provided	2016-03-14	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV000626744	SCV000747447	pathogenic	Talipes equinovarus; Encephalocele; Postaxial polydactyly type A1; Polycystic kidney dysplasia; Oligohydramnios; Microcephaly; Narrow chest	2017-01-01	criteria provided, single submitter	clinical testing
Invitae	RCV000696362	SCV000824920	pathogenic	Joubert syndrome; Meckel-Gruber syndrome	2018-06-01	criteria provided, single submitter	clinical testing	This sequence change, c.4179+1delG, affects a donor splice site in intron 33 of the CC2D2A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs386833761, ExAC 0.02%). This variant has been observed on the opposite chromosome (in trans) from other pathogenic variants in an individuals affected with Joubert syndrome (PMID: 26092869) and Meckel-Gruber syndrome (PMID: 19777577). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 56312). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CC2D2A are known to be pathogenic (PMID: 19777577). For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049724	SCV000082131	probable-pathogenic	Meckel syndrome type 6		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049724	SCV000082132	probable-pathogenic	Meckel syndrome type 6		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.