Submissions for variant NM_206933.4(USH2A):c.13811+3A>G

dbSNP: rs760716728

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001326776	SCV001517826	uncertain significance	not provided	2022-06-28	criteria provided, single submitter	clinical testing	This sequence change falls in intron 63 of the USH2A gene. It does not directly change the encoded amino acid sequence of the USH2A protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs760716728, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1026341). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844285	SCV002104156	uncertain significance	not specified	2022-02-23	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.13811+3A>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 250956 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.13811+3A>G in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab	RCV003446709	SCV004173910	uncertain significance	Retinitis pigmentosa 39	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001831021	SCV004173911	uncertain significance	Usher syndrome type 2A	2023-04-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001831021	SCV002088245	uncertain significance	Usher syndrome type 2A	2020-10-15	no assertion criteria provided	clinical testing