Submissions for variant NM_001378615.1(CC2D2A):c.1766G>A (p.Arg589Lys)

gnomAD frequency: 0.00009  dbSNP: rs763477416

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001245379	SCV001418662	uncertain significance	Familial aplasia of the vermis; Meckel-Gruber syndrome	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 589 of the CC2D2A protein (p.Arg589Lys). This variant is present in population databases (rs763477416, 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: 969922). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
PreventionGenetics, part of Exact Sciences	RCV004538517	SCV004116006	uncertain significance	CC2D2A-related disorder	2023-04-28	criteria provided, single submitter	clinical testing	The CC2D2A c.1766G>A variant is predicted to result in the amino acid substitution p.Arg589Lys. This variant has been reported as a variant of uncertain significance in an individual with retinal/optic disc nerve disease (Table S12 Diñeiro et al 2020. PubMed ID: 32483926). This variant is reported in 0.032% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-15539523-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Fulgent Genetics, Fulgent Genetics	RCV005029830	SCV005660560	uncertain significance	Meckel syndrome, type 6; Joubert syndrome 9; COACH syndrome 2; Retinitis pigmentosa 93	2024-01-30	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001729820	SCV001979239	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001729820	SCV001979970	likely benign	not provided		no assertion criteria provided	clinical testing