Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001266608 | SCV001444784 | likely pathogenic | Inborn genetic diseases | 2020-04-15 | criteria provided, single submitter | clinical testing | The alteration is predicted to abolish the native donor splice site: The c.3203+1G>A intronic alteration results from a G to A substitution one nucleotide after coding exon 14 of the AFF2 gene. Based on BDGP and ESEfinder splice site in silico tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay (Maquat, 2004). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the AFF2 c.3203+1G>A alteration was not observed, with coverage at this position. The altered nucleotide is conserved throughout evolution: The c.3203+1G nucleotide is conserved in available vertebrate species. Based on the available evidence, this alteration is classified as likely pathogenic. |