ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.9110G>A (p.Arg3037His)

gnomAD frequency: 0.00005  dbSNP: rs533700989
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Total submissions: 8
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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 RCV000218151 SCV000269952 benign not specified 2015-02-20 criteria provided, single submitter clinical testing p.Arg3037His in exon 46 of USH2A: This variant is not expected to have clinical significance because it has been identified in 0.7% (109/16492) of South Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs533700989), and due to a lack of conservation across species, incl uding mammals. Of note, 10 have a histidine (His) at this position despite high nearby amino acid conservation.
GeneDx RCV000766324 SCV000581975 likely benign not provided 2021-01-19 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25275298)
Invitae RCV000766324 SCV001064080 benign not provided 2024-01-29 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001276961 SCV001737336 uncertain significance Usher syndrome type 2A 2021-06-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000218151 SCV002819376 uncertain significance not specified 2022-12-08 criteria provided, single submitter clinical testing Variant summary: USH2A c.9110G>A (p.Arg3037His) results in a non-conservative amino acid change located in the Fibronectin type III (IPR003961) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00079 in 249924 control chromosomes, predominantly at a frequency of 0.006 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in USH2A causing Usher Syndrome (0.00079 vs 0.011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.9110G>A in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, with one laboratory classifying it as uncertain significance and four as benign or likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity RCV000766324 SCV003828085 uncertain significance not provided 2020-03-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004541321 SCV004778100 likely benign USH2A-related disorder 2019-09-18 criteria provided, single submitter 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).
Natera, Inc. RCV001276961 SCV001463654 likely benign Usher syndrome type 2A 2020-06-03 no assertion criteria provided clinical testing

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