Submissions for variant NM_000141.5(FGFR2):c.940-2A>G

dbSNP: rs1057519041

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000415479	SCV000328382	pathogenic	Pfeiffer syndrome	2016-09-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000558628	SCV000659624	pathogenic	FGFR2-related craniosynostosis	2023-01-11	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. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in FGFR2 cause disease. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Pfeiffer syndrome (PMID: 7795583, 16418739, 25271085, 270283566). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 374814). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001559997	SCV001782326	pathogenic	not provided	2024-04-08	criteria provided, single submitter	clinical testing	Canonical splice site variant in a gene for which loss-of-function is not a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11781872, 16010693, 11325814, 11173845, 10394936, 27028366, 10731087, 34358384, 7795583, 33502061, 36292735, 24127277, 16418739, 25271085)
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000415479	SCV004807327	uncertain significance	Pfeiffer syndrome	2024-03-26	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796173	SCV005418479	pathogenic	Acrocephalosyndactyly type I; Beare-Stevenson cutis gyrata syndrome; Jackson-Weiss 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; LADD syndrome 1		criteria provided, single submitter	clinical testing	PVS1+PM2_Supporting+PS4+PM6
Clinical Genetics Laboratory, Federal University of Health Sciences of Porto Alegre	RCV000415479	SCV000996314	pathogenic	Pfeiffer syndrome	2014-03-14	no assertion criteria provided	research