Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001863471 | SCV002109357 | uncertain significance | Familial aplasia of the vermis; Meckel-Gruber syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 670 of the CC2D2A protein (p.Glu670Asp). This variant is present in population databases (rs763596840, gnomAD 0.02%). 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: 1353555). 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. 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. |
| Victorian Clinical Genetics Services, |
RCV002272505 | SCV002557363 | likely pathogenic | Joubert syndrome 9 | 2024-10-10 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Joubert syndrome 9, (MIM#612285); Meckel syndrome 6 (MIM#612284) and COACH syndrome (MIM#216360). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to aspartic acid. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 4 heterozygotes, 0 homozygotes). (SP) 0309 - Multiple alternative amino acid changes at the same position have been observed in gnomAD (v4) (highest allele count: 2 heterozygotes, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and high conservation. (I) 0600 - Variant is located in the annotated CC2D2A N-terminal C2 domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. It has been classified as a VUS by a diagnostic laboratory in ClinVar. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1201 - Heterozygous variant detected in trans with a pathogenic heterozygous variant (NM_001080522.2:c.3289del; p.(Val1097Phefs*2)) in a recessive disease. (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Ambry Genetics | RCV004611894 | SCV005098317 | uncertain significance | Inborn genetic diseases | 2024-03-31 | criteria provided, single submitter | clinical testing | The c.2010G>C (p.E670D) alteration is located in exon 18 (coding exon 16) of the CC2D2A gene. This alteration results from a G to C substitution at nucleotide position 2010, causing the glutamic acid (E) at amino acid position 670 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |