ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.486-1G>C

dbSNP: rs876657730
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000220465 SCV000271471 pathogenic Rare genetic deafness 2015-11-19 criteria provided, single submitter clinical testing The c.486-1G>C variant in USH2A has been reported in at least one individual wit h hearing loss (Cremers 2007), and was absent from large population studies. Thi s variant occurs in the invariant region (- 1,2) of the splice consensus sequenc e and is predicted to cause altered splicing leading to an abnormal or absent pr otein. Loss of function of the USH2A gene is an established disease mechanism in Usher syndrome. In summary, this variant meets our criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the predicted impact of the variant.
GeneDx RCV000578546 SCV000680587 pathogenic not provided 2017-11-28 criteria provided, single submitter clinical testing The c.486-1 G>C splice site variant in the USH2A gene has been previously reported in association with Usher syndrome (Cremers et al., 2007; Neuhaus et al., 2017). This variant destroys the canonical splice acceptor site in intron 2, and is expected to cause abnormal gene splicing. The c.486-1 G>C variant is not observed in large population cohorts (Lek et al., 2016). Based on currently available evidence, we consider c.486-1G>C to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000578546 SCV003524119 pathogenic not provided 2022-09-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 228413). Disruption of this splice site has been observed in individuals with USH2A-related conditions (PMID: 24154662, 32037395). This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change affects an acceptor splice site in intron 2 of the USH2A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381).
Baylor Genetics RCV000667749 SCV004207709 pathogenic Retinitis pigmentosa 39 2023-10-28 criteria provided, single submitter clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV001097550 SCV004805054 pathogenic Usher syndrome type 2A 2024-03-17 criteria provided, single submitter research
Counsyl RCV000667749 SCV000792248 likely pathogenic Retinitis pigmentosa 39 2017-06-13 no assertion criteria provided clinical testing
Natera, Inc. RCV001097550 SCV002094028 pathogenic Usher syndrome type 2A 2020-08-27 no assertion criteria provided clinical testing

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