Submissions for variant NM_000128.4(F11):c.218+4A>G

dbSNP: rs767240420

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000579337	SCV000680953	uncertain significance	not provided	2017-12-07	criteria provided, single submitter	clinical testing	The c.218+4A>G variant in the F11 gene has been reported previously in association with factor XI deficiency, in affected individuals who homozygous or heterozygous for the c.218+4A>G variant (Kawankar et al., 2016). This variant reduces the quality of the splice donor site in intron 3, and is expected to cause abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of c.218+4A>G in this individual is unknown. The c.218+4A>G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.218+4A>G as a variant of uncertain significance.
Counsyl	RCV000668645	SCV000793279	uncertain significance	Hereditary factor XI deficiency disease	2017-08-08	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	RCV000668645	SCV003935002	likely pathogenic	Hereditary factor XI deficiency disease	2023-06-23	criteria provided, single submitter	clinical testing	The homozygous c.218+4A>G intronic variant has been identified in a proband with low factor XI levels and has shown prolonged activated partial thromboplastin time. This variant has been observed in 0.0004% gnomAD (aggregated) database (PM2_Moderate). Splice site predictors have predicted to cause deleterious effect (PP3_moderate). PMID: 27710856 has reported this variant previously in 2016.
Natera, Inc.	RCV001834827	SCV002084905	uncertain significance	Plasma factor XI deficiency	2020-03-03	no assertion criteria provided	clinical testing