Submissions for variant NM_001378615.1(CC2D2A):c.3364C>T (p.Pro1122Ser)

dbSNP: rs118204051

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
UW Hindbrain Malformation Research Program, University of Washington	RCV000000779	SCV000256330	pathogenic	Joubert syndrome 9	2015-02-23	criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000730543	SCV000858288	likely pathogenic	not provided	2017-11-28	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000000779	SCV001164435	uncertain significance	Joubert syndrome 9	2018-12-03	criteria provided, single submitter	research	The homozygous p.Pro1122Ser variant in CC2D2A was identified by our study in one individual with Joubert syndrome. The p.Pro1122Ser variant in CC2D2A has been reported in at least 5 Saudi Arabian individuals with Joubert syndrome (PMID: 26092869, 18950740), and has been identified in 0.01951% (1/5126) of other chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although there is some suspicion of pathogenicity, the clinical significance of the p.Pro1122Ser variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PM1_Supporting (Richards 2015).
Baylor Genetics	RCV001329602	SCV001521087	likely pathogenic	COACH syndrome 1	2019-11-14	criteria provided, single submitter	clinical testing	This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing by following sources [PMID: 29620724, 18950740, ClinVar ID: 743]
Invitae	RCV001851514	SCV002237108	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome	2022-03-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt CC2D2A protein function. ClinVar contains an entry for this variant (Variation ID: 743). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 18950740). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs118204051, gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1122 of the CC2D2A protein (p.Pro1122Ser).
Revvity Omics, Revvity	RCV000730543	SCV003820484	likely pathogenic	not provided	2022-05-17	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000000779	SCV004804917	likely pathogenic	Joubert syndrome 9	2024-03-17	criteria provided, single submitter	research
OMIM	RCV000000779	SCV000020929	pathogenic	Joubert syndrome 9	2008-11-01	no assertion criteria provided	literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000000779	SCV001132927	pathogenic	Joubert syndrome 9	2019-08-25	no assertion criteria provided	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV000000779	SCV003927889	likely pathogenic	Joubert syndrome 9	2023-04-01	no assertion criteria provided	clinical testing