Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002314394 | SCV000847905 | benign | Inborn genetic diseases | 2023-12-18 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV000889161 | SCV001032823 | likely benign | not provided | 2024-03-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000889161 | SCV001988021 | uncertain significance | not provided | 2019-08-05 | criteria provided, single submitter | clinical testing | Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |
| Centogene AG - |
RCV001809779 | SCV002059686 | uncertain significance | Intellectual disability, autosomal recessive 3 | 2019-05-21 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387918 | SCV004099660 | uncertain significance | not specified | 2024-09-04 | criteria provided, single submitter | clinical testing | Variant summary: CC2D1A c.1357-2A>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of CC2D1A function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00028 in 1557190 control chromosomes, predominantly at a frequency of 0.005 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in CC2D1A causing Intellectual Disability 3 phenotype. To our knowledge, no occurrence of c.1357-2A>C in individuals affected with Intellectual Disability 3 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 588298). Based on the evidence outlined above, the variant was classified as uncertain significance. |