Submissions for variant NM_020800.3(IFT80):c.869dup (p.Asn290fs)

dbSNP: rs773858865

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413805	SCV000492168	pathogenic	not provided	2016-11-21	criteria provided, single submitter	clinical testing	The c.869dupA pathogenic variant in the IFT80 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.869dupA variant causes a frameshift starting with codon Asparagine 290, changes this amino acid to a Lysine residue, and creates a premature Stop codon at position 33 of the new reading frame, denoted p.Asn290LysfsX33. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.869dupA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.869dupA as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002524657	SCV002997048	pathogenic	Jeune thoracic dystrophy	2022-08-09	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 373566). This variant has not been reported in the literature in individuals affected with IFT80-related conditions. This variant is present in population databases (rs773858865, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Asn290Lysfs*33) in the IFT80 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IFT80 are known to be pathogenic (PMID: 21227999, 23339108, 29068549).