ClinVar Miner

Submissions for variant NM_000141.4(FGFR2):c.940-2A>G (rs1057519041)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000415479 SCV000328382 pathogenic Pfeiffer syndrome 2016-09-17 criteria provided, single submitter clinical testing
Invitae RCV000558628 SCV000659624 pathogenic FGFR2 related craniosynostosis 2017-12-08 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 7 of the FGFR2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple unrelated individuals with Pfeiffer syndrome (PMID: 25271085, 16418739, 7795583) and Apert syndrome (PMID: 270283566). It has also been reported to segregate with disease in at least one family (PMID: 7795583). ClinVar contains an entry for this variant (Variation ID: 374814). In summary, although the effect of this variant on protein function has not been reported in functional studies, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547). While the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in FGFR2 as a whole cause disease, this particular variant is absent from the general population and has been reported in several affected individuals and families. Therefore, it has been classified as Pathogenic.

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