Submissions for variant STAT3:c.469-34_469-30del

dbSNP: rs140846959

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001574812	SCV001801688	likely benign	not provided	2018-07-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844019	SCV002104082	benign	not specified	2022-02-22	criteria provided, single submitter	clinical testing	Variant summary: STAT3 c.469-34_469-30delTACTT is located at a position not widely known to affect splicing. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0022 in 246318 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately significantly higher than the estimated maximal expected allele frequency for a pathogenic variant in STAT3 causing Hyper IgE Syndrome phenotype (2.2e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.469-34_469-30delTACTT in individuals affected with Hyper IgE Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.