Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589352 | SCV000695659 | likely benign | not provided | 2016-06-10 | criteria provided, single submitter | clinical testing | Variant summary: The c.2646+55G>T in GAA gene is an intronic variant that affects a non-conserved nucleotide located at a position not widely known to affect splicing. One in silico tool predicts a benign outcome for this variant. 5/5 in silico splicing tools predict no significant effects on splicing, however these predictions have yet to be confirmed by in vitro/vivo studies. This variant was found in 11/5008 control chromosomes from the 1000G control database (coverage of this region in ExAC was too low to be reliable), predominantly observed in the European subpopulation at a frequency of 0.0099 (10/1006). This frequency is over two times the estimated maximal expected allele frequency of a pathogenic GAA variant (0.0042205), suggesting this is likely a benign polymorphism found primarily in the populations of European origin. The variant was not reported in affected individuals in published reports or clinical diagnostic centers. Taken together, based on the prevalence in the general population and lack of a predicted effect on splicing, the variant was classified as Likely Benign. |