Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV003448558 | SCV004176034 | uncertain significance | Arrhythmogenic right ventricular dysplasia 13 | 2023-05-17 | criteria provided, single submitter | clinical testing | This is an approximately 156kb heterozygous copy number loss located on the long arm of chromosome 10 (10q21.3). The deleted region (chr10:66466571-66622564) encompasses exons 10 and 11 of the CTNNA3 gene as well as surrounding and intervening intronic sequences. This variant is expected to alter the wild-type translational reading frame and is expected to result in loss-of-function via nonsense-mediated decay of the encoded protein (NM_013266.4:c.1282-780_1531+54046del). Similar intergenic deletions in the CTNNA3 gene have been reported individuals with dilated cardiomyopathy however with uncertain clinical significance, and one of the reported individuals with the CTNNA3 deletion was also found to harbor a canonical splice variant in the FLNCgene [PMID: 35288587]. While this exact variant is absent from population databases, several overlapping deletions are observed in in gnomAD SVs(v2.1) with low frequency. While the exact deletion identified here is absent from ClinVar, one deletion fully contained within the one identified here is reported as a Variant of Uncertain Significance (VarID:474805). Based on available evidence this ~156kb copy number loss identified in the CTNNA3 gene is classified as a Variant of Uncertain Significance. |