ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.15433G>A (p.Val5145Ile) (rs111033269)

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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 RCV000787986 SCV000927010 benign Usher syndrome 2019-01-14 reviewed by expert panel curation The p.Val5145Ile variant in USH2A has been identified in at least 5 individuals with Usher syndrome; however, in 3 individuals no variant on the second allele was identified and in two individuals, no information about the other allele was provided (PMIDs 28041643, 25999674, 20829743, 27353947, 23591405). Additionally, the p.Val5145Ile variant was identified in 2 alleles of 56 retinitis pigmentosa patients, however it is unclear in which one or two patients these alleles were found (PMID 20591486). The filtering allele frequency of the p.Val5145Ile variant in the USH2A gene is 0.7% for European (Finnish) chromosomes by gnomAD (201/25124 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). Additionally, computational prediction analysis using the metapredictor tool REVEL suggests that the variant may not impact the protein (BP4) .In summary, this variant meets criteria to be classified as benign based primarily on population frequency data and the absence of cases with biallelic variants. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BA1, BP4.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041787 SCV000065483 benign not specified 2013-08-16 criteria provided, single submitter clinical testing Val5145Ile in exon 71 of USH2A: This variant has been identified in one individu al with Usher syndrome or nonsyndromic retinitis pigmentosa and two individuals with nonsyndromic retinitis pigmentosa (van Wijk - unpublished data, McGee 2010, Clark 2010). However, it was not noted if any of these individuals had a second USH2A variant. In addition, this variant has also been identified in one proban d with Fundus albipunctatus who was homozygous for a null mutation in another ge ne (Schatz 2010). It has also been identified by our laboratory in two probands who have other etiologies for their hearing loss. Furthermore, this variant is n ot expected to have clinical significance because it has been identified in 0.6% (48/8600) of European American chromosomes by the NHLBI Exome Sequencing Projec t (; dbSNP rs111033269). In summary, this varia nt meets our criteria to be classified as benign.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000041787 SCV000232402 benign not specified 2014-12-17 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585242 SCV000692661 likely benign not provided 2018-05-01 criteria provided, single submitter clinical testing
GeneDx RCV000585242 SCV000730484 benign not provided 2019-03-25 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 20591486, 20507924, 30245029, 23591405, 26927203, 32707200, 32581362)
Invitae RCV000585242 SCV001034273 benign not provided 2020-12-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000041787 SCV001159086 benign not specified 2018-10-02 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504930 SCV000598793 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000504930 SCV000926912 uncertain significance Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Natera, Inc. RCV001271907 SCV001453401 likely benign Usher syndrome, type 2A 2020-06-13 no assertion criteria provided clinical testing

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