ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.6751T>A (p.Ser2251Thr)

gnomAD frequency: 0.00001  dbSNP: rs750302027
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001363353 SCV001559461 uncertain significance not provided 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 2251 of the USH2A protein (p.Ser2251Thr). This variant is present in population databases (rs750302027, gnomAD 0.002%). 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: 1054782). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt USH2A protein function with a negative predictive value of 95%. 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.
GeneDx RCV001363353 SCV002001292 uncertain significance not provided 2021-07-14 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Genome-Nilou Lab RCV003450014 SCV004181619 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001836362 SCV004181620 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV004036876 SCV004975830 uncertain significance Inborn genetic diseases 2024-01-02 criteria provided, single submitter clinical testing The c.6751T>A (p.S2251T) alteration is located in exon 35 (coding exon 34) of the USH2A gene. This alteration results from a T to A substitution at nucleotide position 6751, causing the serine (S) at amino acid position 2251 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001836362 SCV002090872 uncertain significance Usher syndrome type 2A 2020-06-03 no assertion criteria provided clinical testing

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