Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genomic Diagnostic Laboratory, |
RCV000415495 | SCV000328403 | likely pathogenic | Pfeiffer syndrome | 2016-09-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549391 | SCV001769532 | pathogenic | not provided | 2022-11-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28166054, 23754559, 11781872, 23908597, 32139749) |
| Labcorp Genetics |
RCV001865307 | SCV002241269 | pathogenic | FGFR2-related craniosynostosis | 2024-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 565 of the FGFR2 protein (p.Glu565Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Pfeiffer syndrome (PMID: 11781872). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 374823). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FGFR2 protein function with a positive predictive value of 80%. This variant disrupts the p.Glu565 amino acid residue in FGFR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15523615, 18541976, 24127277). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002488862 | SCV002794740 | likely 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; Familial scaphocephaly syndrome, McGillivray type; Bent bone dysplasia syndrome 1; Gastric cancer | 2022-03-08 | criteria provided, single submitter | clinical testing | |
| Servicio de Genética Del Instituto Nacional de Salud Del Niño, |
RCV000415495 | SCV005414451 | pathogenic | Pfeiffer syndrome | 2024-11-18 | criteria provided, single submitter | clinical testing | The variant NM_000141.5:c.1694A>G (p.Glu565Gly) results in a glutamic acid-to-glycine substitution at codon 565. Based on available evidence, this variant meets the criteria for PS4, PP3, PM2, PM5, PP2, and PP5, supporting its classification as pathogenic. These criteria are based on the impact of the variant on protein function, the presence of similar pathogenic variants, and computational predictions suggesting a damaging effect. |