Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000686087 | SCV000813590 | pathogenic | Anophthalmia/microphthalmia-esophageal atresia syndrome | 2018-04-11 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SOX2-related disease. For these reasons, this variant has been classified as Pathogenic. Other frameshift variants (p.Ala281Argfs*87, p.Leu314Serfs*57, p.Pro302Argfs*69) that lie downstream of this variant and result in a similarly extended protein product have been reported in individuals affected with microphthalmia  (PMID: 24498598, 19921648, 24211324). In addition, a missense variant (p.Ala287Pro) that lies downstream of this variant has been reported in an individual affected with microphthalmia (PMID: 19921648). This sequence change deletes 20 nucleotides and inserts 7 nucleotides from exon 1 of the SOX2 mRNA (c.841_860delinsACCTCGG), causing a frameshift at codon 281. This creates a frameshift in the SOX2 mRNA (p.Ala281Thrfs*86). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acids of the SOX2 protein, and to extend the protein by an additional 48 amino acids. |