Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001267074 | SCV001445255 | likely pathogenic | Inborn genetic diseases | 2021-01-15 | criteria provided, single submitter | clinical testing | The c.4583-2A>G intronic variant results from an A to G substitution two nucleotides before exon 19 (coding exon 19) of the TNRC6B gene. Alterations that disrupt the canonical splice acceptor site are typically deleterious in nature (Richards, 2015). Alterations that disrupt the canonical splice site are expected to result in aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD), the TNRC6B c.4583-2A>G alteration was not observed, with coverage at this position. The c.4583-2A nucleotide is conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Based on the available evidence, this alteration is classified as likely pathogenic. |