ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.4714C>T (p.Leu1572Phe) (rs111033333)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001261016 SCV001438404 likely benign Usher syndrome 2019-07-28 reviewed by expert panel curation The p.Leu1572Phe variant in USH2A gene has a filtering allele frequency= 0.12% in Latino in gnomAD (54/35388 with 95% CI) 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). It was reported in multiple publications as a polymorphism or as non-pathogenic based on detection among normal control chromosomes or other evidence (PMID: 18273898, 19881469 and 17085681). Although the variant was reported in trans with c.2299delG in one patient diagnosed with Usher syndrome type II and in another with unclassified Usher syndrome (PMID: 25097241 and 28944237), it was also identified in cis with c.2299delG; p.Glu767Serfs and in unknown configuration with c.2299delG and a stop codon (PMID: 25472526), both in patients with Usher syndrome type II (BP2; PMID: 20507924, 25097241, 17405132 and 26969326). Computational prediction using REVEL was 0.65 which did not meet the Hearing Loss Expert Panel (HL EP) specified threshold of >0.7 for PP3. In summary, this variant meets criteria to be classified as likely benign for autosomal recessive Usher syndrome, type 2A based on the HL EP-specified ACMG/AMP criteria applied (BS1, BP2).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041847 SCV000065543 benign not specified 2008-01-08 criteria provided, single submitter clinical testing
GeneDx RCV000087011 SCV000169742 likely benign not provided 2020-09-30 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25472526, 25097241, 22025579, 26667666, 26969326, 28944237, 20145675, 22004887, 11311042, 17085681, 29953849, 30245029, 33576794)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000041847 SCV000227976 benign not specified 2014-11-22 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000087011 SCV000493417 likely benign not provided 2019-08-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000624538 SCV000740744 uncertain significance Inborn genetic diseases 2014-10-13 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000041847 SCV000884851 benign not specified 2018-07-31 criteria provided, single submitter clinical testing
Invitae RCV000087011 SCV001025598 likely benign not provided 2020-12-03 criteria provided, single submitter clinical testing
NEI Ophthalmic Genomics Laboratory,National Institutes of Health RCV000087011 SCV000119264 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504950 SCV000598813 likely benign Retinitis pigmentosa 2015-01-01 no assertion criteria provided research

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