ClinVar Miner

Submissions for variant NM_022970.3(FGFR2):c.1087+1303T>C (rs121918488)

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Total submissions: 7
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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 RCV000014178 SCV000328390 pathogenic Pfeiffer syndrome 2016-09-17 criteria provided, single submitter clinical testing
Invitae RCV000534888 SCV000659602 pathogenic FGFR2 related craniosynostosis 2018-09-06 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 342 of the FGFR2 protein (p.Cys342Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Crouzen or Pfeiffer syndromes (PMID: 7987400, 24127277 25759925 12884424). ClinVar contains an entry for this variant (Variation ID: 13266). Multiple different missense substitutions at this codon (p.Cys342Ser, p.Cys342Tyr, p.Cys342Trp) have been determined to be pathogenic (PMID: 24127277). This suggests that the cysteine residue is critical for FGFR2 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Johns Hopkins Genomics,Johns Hopkins University RCV000014178 SCV000998474 pathogenic Pfeiffer syndrome 2019-08-27 criteria provided, single submitter clinical testing This previously reported FGFR2 variant (rs121918488) is absent from large population datasets. Two submitters in ClinVar classify this variant as pathogenic. Multiple different missense changes have been reported in the same residue that have been shown to affect protein functionality. Two bioinformatic tools queried predict that the substitution would be possibly damaging, but these algorithms have low specificity, especially for predicting gain of function variants. This variant is considered pathogenic.
OMIM RCV000014177 SCV000034425 pathogenic Crouzon syndrome 2000-01-01 no assertion criteria provided literature only
OMIM RCV000014178 SCV000034426 pathogenic Pfeiffer syndrome 2000-01-01 no assertion criteria provided literature only
OMIM RCV000014179 SCV000034427 pathogenic Jackson-Weiss syndrome 2000-01-01 no assertion criteria provided literature only
OMIM RCV000014180 SCV000034428 pathogenic Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 2000-01-01 no assertion criteria provided literature only

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