Submissions for variant NM_206933.4(USH2A):c.10609C>T (p.Leu3537Phe)

gnomAD frequency: 0.00046  dbSNP: rs138656755

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522433	SCV000620271	uncertain significance	not provided	2017-08-24	criteria provided, single submitter	clinical testing	The L3537F variant in the USH2A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L3537F variant is observed in 9/10356 (0.087%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). The L3537F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L3537F as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000522433	SCV001197742	likely benign	not provided	2025-01-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004732929	SCV005347382	uncertain significance	USH2A-related disorder	2024-08-27	no assertion criteria provided	clinical testing	The USH2A c.10609C>T variant is predicted to result in the amino acid substitution p.Leu3537Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.15% of alleles in individuals of African descent in gnomAD, which is likely too frequent to be a primary cause of disease. Although we suspect that this variant may be benign, its clinical significance is currently classified as uncertain due to the absence of conclusive functional and genetic evidence.