Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001370586 | SCV001567107 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-03-11 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 100 of the CC2D2A protein (p.Met100Leu). This variant is present in population databases (rs370014549, gnomAD 0.01%). 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: 1061071). 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 not expected to disrupt 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. |
Gene |
RCV001776230 | SCV002013534 | uncertain significance | not provided | 2023-05-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Fulgent Genetics, |
RCV002488165 | SCV002784874 | uncertain significance | Meckel syndrome, type 6; Joubert syndrome 9; COACH syndrome 2; Retinitis pigmentosa 93 | 2024-05-23 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003169907 | SCV003869332 | uncertain significance | Inborn genetic diseases | 2023-01-18 | criteria provided, single submitter | clinical testing | The c.298A>C (p.M100L) alteration is located in exon 6 (coding exon 4) of the CC2D2A gene. This alteration results from a A to C substitution at nucleotide position 298, causing the methionine (M) at amino acid position 100 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |