Submissions for variant NM_014425.5(INVS):c.2068+2T>C

gnomAD frequency: 0.00002  dbSNP: rs777556837

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002046047	SCV002303860	likely pathogenic	Nephronophthisis	2024-08-19	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 13 of the INVS gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs777556837, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with INVS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1514009). Studies have shown that disruption of this splice site results in skipping of exon 13 and part of exon 14, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 11935322). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005050522	SCV005679544	likely pathogenic	Infantile nephronophthisis	2024-02-14	criteria provided, single submitter	clinical testing