ClinVar

Description

Variant summary: SLC26A4 c.2091T>G (p.Asp697Glu) results in a conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant is also close to the canonical acceptor site of Intron 18. Several computational tools predict a significant impact on normal splicing: Two predict the variant weakens the 3' canonical acceptor site. One predict the variant creates a 3' cryptic acceptor site. One predict the variant no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251228 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2091T>G in individuals affected with Pendred Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.