Submissions for variant NM_001378615.1(CC2D2A):c.4506A>C (p.Lys1502Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002800651	SCV003033564	uncertain significance	Familial aplasia of the vermis; Meckel-Gruber syndrome	2022-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1502 of the CC2D2A protein (p.Lys1502Asn). This variant is present in population databases (rs201316005, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with CC2D2A-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CC2D2A protein function. 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	RCV004733533	SCV005360547	uncertain significance	CC2D2A-related disorder	2024-09-24	no assertion criteria provided	clinical testing	The CC2D2A c.4506A>C variant is predicted to result in the amino acid substitution p.Lys1502Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0089% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.