Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV002266785 | SCV002548886 | uncertain significance | Autism spectrum disorder due to AUTS2 deficiency | 2021-08-12 | criteria provided, single submitter | clinical testing | The c.1673C>T (p.Thr558Met) variant identified in the AUTS2 gene substitutes a well conserved Threonine for Methionine at amino acid 558/1260(exon 9/19). This variant is found with low frequency in gnomAD(v2.1.1)(3 heterozygotes, 0 homozygotes; allele frequency: 1.21e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.026) and Benign (REVEL;score:0.2189) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Thr558 residue is not within a mapped domain of AUTS2 (UniProtKB:Q8WXX7). Given the lack of compelling evidence for its pathogenicity, the c.1673C>T (p.Thr558Met) variant identified in the AUTS2 gene is reported as a Variant of Uncertain Significance. |