Submissions for variant NM_206933.4(USH2A):c.8845+6_8845+9del

dbSNP: rs541344995

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000216065	SCV000272901	uncertain significance	not specified	2015-02-26	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The c.8845+6_8845+9 delTAAG variant in USH2A has not been previously reported in individuals with he aring loss. This variant has been identified in 0.2% (16/10578) of African chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs541344995). Although this variant has been seen in the general popul ation, its frequency is not high enough to rule out a pathogenic role. This vari ant is located in the 5' splice region. Computational tools do not suggest an im pact to splicing at the native 5' donor splice site. However, this information i s not predictive enough to rule out pathogenicity. In summary, while the clinica l significance of the c.8845+6_8845+9delTAAG variant is uncertain, the frequency data suggest that it is more likely to be benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001239051	SCV001411896	uncertain significance	not provided	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change falls in intron 44 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 (rs541344995, gnomAD 0.2%). 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: 229628). 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 may create or strengthen a splice site. 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	RCV003445714	SCV004172058	uncertain significance	Retinitis pigmentosa 39	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001276964	SCV004172059	uncertain significance	Usher syndrome type 2A	2023-04-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001276964	SCV001463657	uncertain significance	Usher syndrome type 2A	2020-01-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004541344	SCV004767713	likely benign	USH2A-related disorder	2024-03-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).