Submissions for variant NM_031471.6(FERMT3):c.1312-2A>C

gnomAD frequency: 0.00003  dbSNP: rs760261349

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001218117	SCV001389989	likely pathogenic	Leukocyte adhesion deficiency 3	2019-07-04	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FERMT3 are known to be pathogenic (PMID: 19064721, 19234463, 22134107). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice dinucleotide site has been observed in an individual affected with leukocyte adhesion deficiency III (PMID: 22564402). This variant is present in population databases (rs760261349, ExAC 0.01%). This sequence change affects an acceptor splice site in intron 11 of the FERMT3 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.