Submissions for variant NM_001363711.2(DUOX2):c.4524+1G>C

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004800071	SCV005423420	likely pathogenic	Thyroid dyshormonogenesis 6	2024-10-04	criteria provided, single submitter	clinical testing	Variant summary: DUOX2 c.4524+1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of DUOX2 function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 249208 control chromosomes. To our knowledge, no occurrence of c.4524+1G>C in individuals affected with Thyroid Dyshormonogenesis 6 and no experimental evidence demonstrating its impact on protein function have been reported. At-least one missense variant in Exon 34 has been associated with disease in ClinVar (c.4552G>A p.Gly1518Ser). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.