Submissions for variant NM_001378615.1(CC2D2A):c.3014+4A>C

gnomAD frequency: 0.00014  dbSNP: rs748451478

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000435852	SCV000534046	likely benign	not specified	2016-11-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000524961	SCV000634589	uncertain significance	Familial aplasia of the vermis; Meckel-Gruber syndrome	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change falls in intron 24 of the CC2D2A gene. It does not directly change the encoded amino acid sequence of the CC2D2A protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs748451478, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CC2D2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 391066). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002522611	SCV003548011	uncertain significance	Inborn genetic diseases	2023-08-15	criteria provided, single submitter	clinical testing	The c.3014+4A>C intronic alteration consists of a A to C substitution nucleotides after coding exon 22 in the CC2D2A gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV005033954	SCV005662450	uncertain significance	Meckel syndrome, type 6; Joubert syndrome 9; COACH syndrome 2; Retinitis pigmentosa 93	2024-05-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004533116	SCV004730168	likely benign	CC2D2A-related disorder	2023-09-08	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).