ClinVar Miner

Submissions for variant NM_022970.3(FGFR2):c.1087+1363_1087+1364insTCAACA (rs1554928786)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000655415 SCV000777345 uncertain significance FGFR2 related craniosynostosis 2017-10-27 criteria provided, single submitter clinical testing This sequence change inserts 6 nucleotides at the exon 8 / intron 8 junction of the FGFR2 gene (c.1084_1084+1insTCAACA). This disrupts the sequence that constitute the consensus donor splice site. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Pfieffer syndrome in a single family (PMID: 8644708). This variant has also been reported as c.1263insTCAACA. Experimental studies have shown that this insertion inactivates the consensus donor splice site and subsequently activates a cryptic splice site.  Use of this cryptic splice site causes a deletion of 17 amino acids and moves the third immunoglobulin-like domain closer to the transmembrane domain of the resulting FGFR2 protein. However, the functional consequence of the loss of these 17 amino acids on FGFR2 protein function has not been reported (PMID: 8644708). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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