Submissions for variant NM_206933.4(USH2A):c.2167+4C>T

gnomAD frequency: 0.00001  dbSNP: rs200638562

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041808	SCV000065504	uncertain significance	not specified	2011-06-29	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The 2167+4C>T varia nt in USH2A has not been reported in the literature nor previously identified by our laboratory. This variant is located in the 5' splice region but does not af fect the invariant +1 and +2 positions. Although position +4 is part of the spli ce site region, the reference sequence was already divergent from consensus (nor mally an A at this position) and therefore this variant is less likely to disrup t splicing. In summary, the clinical significance of this variant cannot be dete rmined with certainty at this time; however, given that there is currently no ev idence to suggest this variant is pathogenic, we would lean towards a more likel y benign role.
Counsyl	RCV000666387	SCV000790670	uncertain significance	Usher syndrome type 2A; Retinitis pigmentosa 39	2017-03-31	criteria provided, single submitter	clinical testing
Invitae	RCV002513601	SCV003472277	uncertain significance	not provided	2022-03-18	criteria provided, single submitter	clinical testing	This sequence change falls in intron 12 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 (rs200638562, gnomAD 0.006%). 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: 48485). 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.
Genome-Nilou Lab	RCV003445121	SCV004172187	uncertain significance	Retinitis pigmentosa 39	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001275023	SCV004172188	uncertain significance	Usher syndrome type 2A	2023-04-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001275023	SCV001459771	uncertain significance	Usher syndrome type 2A	2020-03-11	no assertion criteria provided	clinical testing