Submissions for variant NM_023110.3(FGFR1):c.92-19G>A

dbSNP: rs753723806

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000494040	SCV000582989	uncertain significance	not provided	2017-05-23	criteria provided, single submitter	clinical testing	The c.92-19 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.92-19 G>A creates a cryptic acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV002524045	SCV003199585	uncertain significance	Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome	2023-12-13	criteria provided, single submitter	clinical testing	This sequence change falls in intron 2 of the FGFR1 gene. It does not directly change the encoded amino acid sequence of the FGFR1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 430230). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.