Submissions for variant NM_001190274.2(FBXO11):c.2720_2721del (p.His907fs)

dbSNP: rs2530936889

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002722780	SCV003556349	likely pathogenic	Inborn genetic diseases	2021-06-16	criteria provided, single submitter	clinical testing	The c.2720_2721delAT (p.H907Rfs*7) alteration, located in exon 23 (coding exon 23) of the FBXO11 gene, consists of a deletion of 2 nucleotides from position 2720 to 2721, causing a translational frameshift with a predicted alternate stop codon after 7 amino acids. This alteration occurs at the 3' terminus of the FBXO11 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 2% of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). Based on data from the Genome Aggregation Database (gnomAD), the FBXO11 c.2720_2721delAT alteration was not observed, with coverage at this position. Based on the available evidence, this alteration is classified as likely pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV003233015	SCV003930363	likely pathogenic	Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities	2023-06-12	criteria provided, single submitter	clinical testing