Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000223330 | SCV000271712 | uncertain significance | not specified | 2015-04-13 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The c.1280+4AG[3] ( also reported as c.1280+4_1280+5delAG) variant in DSG2 has not been previously r eported in individuals with cardiomyopathy, but has been identified in 0.2% (19/ 8616) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http: //exac.broadinstitute.org). This variant results in a deletion of one dinucleoti de repeat in the 5' splice region. Computational tools do not suggest an impact to splicing. However, this information is not predictive enough to rule out path ogenicity. In summary, while the clinical significance of the c.1280+4AG[3] vari ant is uncertain, its frequency suggests that it is more likely to be benign. |
Illumina Laboratory Services, |
RCV000377305 | SCV000408226 | uncertain significance | Dilated Cardiomyopathy, Dominant | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000266431 | SCV000408227 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000223330 | SCV000570740 | likely benign | not specified | 2016-06-24 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590706 | SCV000697881 | likely benign | not provided | 2017-03-06 | criteria provided, single submitter | clinical testing | Variant summary: The DSG2 c.1280+10_1280+11delAG variant involves the alteration of an intronic nucleotide, which 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 19/120602 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.002206 (19/8612). This frequency is about 221 times the estimated maximal expected allele frequency of a pathogenic DSG2 variant (0.00001), suggesting this is likely a benign polymorphism found primarily in population(s) of East Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, without additional information to perform an independent evaluation. Therefore, the variant of interest has been classified as "likely benign." |
Labcorp Genetics |
RCV001078612 | SCV000764004 | likely benign | Arrhythmogenic right ventricular dysplasia 10 | 2024-01-09 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001184745 | SCV001350801 | benign | Cardiomyopathy | 2018-12-03 | criteria provided, single submitter | clinical testing | |
Phosphorus, |
RCV000223330 | SCV002073404 | likely benign | not specified | 2022-01-19 | criteria provided, single submitter | clinical testing | This deletion variant is located 10bp away from the canonical splice-site in intron 9 of the DSG2 gene (transcript: NM_001943.3). This variant has an entry in ClinVar (228628) NM_001943.5(DSG2):c.1280+4AG[3]. This variant occurred in gnomAD with a total MAF of 0.0175% and the highest MAF of 0.2494% in the East Asian population. This position is not conserved. In silico splicing algorithms predicted that this variant will not have an impact on splicing (not found in scSNV). The variant has not occurred in the literature in association with disease. Considering that the variant has a relatively high frequency in the population, it has been classified as Likely Benign. |
Prevention |
RCV003947717 | SCV004764476 | likely benign | DSG2-related disorder | 2020-10-19 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |