ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.15494C>G (p.Ala5165Gly) (rs146892520)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel, RCV000710317 SCV000840503 likely benign Usher syndrome 2018-09-28 reviewed by expert panel curation The filtering allele frequency of the p.Ala5165Gly variant in the USH2A gene is 0.21% (63/24034) of African chromosomes chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein (BP4). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria applied (BS1_Supporting, BP4).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725036 SCV000333400 uncertain significance not provided 2015-07-24 criteria provided, single submitter clinical testing
GeneDx RCV000725036 SCV000572703 uncertain significance not provided 2017-01-30 criteria provided, single submitter clinical testing The A5165G variant in the USH2A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A5165G variant is observed in 25/10404 (0.2%) alleles from individuals of African background, in the ExAC dataset (Lek et al., 2016). The A5165G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A5165G as a variant of uncertain significance.

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