ClinVar

Description

The F11 c.1716+1G>A variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. The c.1716+1G>A variant has been described as a founder mutation in the Ashkenazi Jewish population (Peretz et al. 2013). The c.1716+1G>A variant has been reported in three studies and was found in a total of 30 probands from 14 families of Ashkenazi Jewish descent and one family of unknown ethnicity with factor XI deficiency, including in one in a homozygous state, in 12 in a compound heterozygous state, and in 17 in a heterozygous state (Asakai et al. 1989, Mitchell et al. 2006, Peretz et al. 2013). The c.1716+1G>A variant was shown to segregate with the disease in two studies and was absent from 491 healthy Ashkenazi Jewish controls (Asakai et al. 1989, Peretz et al. 2013). The variant is reported at a frequency of 0.000406 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the evidence and the potential impact of splice donor variants, the c.1716+1G>A variant is classified as pathogenic for Factor XI deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.