Submissions for variant NM_023110.3(FGFR1):c.2292+3A>G

gnomAD frequency: 0.00006  dbSNP: rs747737281

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000644519	SCV000766218	uncertain significance	Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome	2023-10-17	criteria provided, single submitter	clinical testing	This sequence change falls in intron 17 of the FGFR1 gene. It does not directly change the encoded amino acid sequence of the FGFR1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs747737281, gnomAD 0.01%). This variant has been observed in individual(s) with Kallman syndrome (PMID: 23533228). This variant is also known as 2289+6A>G. ClinVar contains an entry for this variant (Variation ID: 536193). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
GeneDx	RCV001548029	SCV001767877	likely benign	not provided	2019-01-24	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23533228)
CeGaT Center for Human Genetics Tuebingen	RCV001548029	SCV004164638	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	FGFR1: BP4, BS2