ClinVar Miner

Submissions for variant NM_022970.3(FGFR2):c.314A>G (p.Tyr105Cys) (rs1434545235)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522502 SCV000616720 pathogenic not provided 2017-12-27 criteria provided, single submitter clinical testing The Y105C variant in the FGFR2 gene has been reported previously in several individuals with Crouzon syndrome (Kan et al., 2002; Lajeunie et al., 2006; Roscioli et al., 2013; Yoo et al., 2014; Goos et al., 2015). This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y105C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, this variant has been observed to occur de novo in affected patients tested at GeneDx. We interpret Y105C as a pathogenic variant.
Invitae RCV000531359 SCV000659616 pathogenic FGFR2 related craniosynostosis 2019-02-25 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 105 of the FGFR2 protein (p.Tyr105Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals with Crouzon syndrome (PMID: 8946174, 24127277, 11781872, 16418739). Family studies have indicated that this variant was not present in the parents of an individual affected with FGFR3-related disease, which suggests that it was de novo in that affected individual (Invitae). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000762805 SCV000893155 pathogenic Acrocephalosyndactyly type I; Beare-Stevenson cutis gyrata syndrome; Jackson-Weiss syndrome; Levy-Hollister syndrome; Pfeiffer syndrome; Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis; Crouzon syndrome; Saethre-Chotzen syndrome; Scaphocephaly, maxillary retrusion, and mental retardation; Neoplasm of stomach; Bent bone dysplasia syndrome 2018-10-31 criteria provided, single submitter clinical testing

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