ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.2187C>A (p.Cys729Ter)

gnomAD frequency: 0.00002  dbSNP: rs757154662
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001074494 SCV001240081 likely pathogenic Retinal dystrophy 2017-10-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001385356 SCV001585189 pathogenic not provided 2024-02-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys729*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is present in population databases (rs757154662, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with Usher syndrome (PMID: 30390381, 30948794). ClinVar contains an entry for this variant (Variation ID: 866467). For these reasons, this variant has been classified as Pathogenic.
3billion, Medical Genetics RCV001809978 SCV002058501 pathogenic Usher syndrome type 2A 2022-01-03 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000866467). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000020, PM2_M). The variant has been reported to be in trans with a pathogenic variant (NM_206933.4:c.9570+1G>A) as compound heterozygous (3billion dataset, PM3_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Genome-Nilou Lab RCV003455368 SCV004182450 likely pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001809978 SCV004182452 likely pathogenic Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV001074494 SCV004708042 pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Baylor Genetics RCV003455368 SCV005055743 pathogenic Retinitis pigmentosa 39 2024-01-11 criteria provided, single submitter clinical testing

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