Submissions for variant NM_206933.4(USH2A):c.6240G>T (p.Lys2080Asn)

gnomAD frequency: 0.00770  dbSNP: rs114402911

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041881	SCV000065577	benign	not specified	2012-05-14	criteria provided, single submitter	clinical testing	Lys2080Asn in Exon 32 of USH2A: This variant is not expected to have clinical si gnificance because it has been identified in 1.1% (41/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs114402911). As expected, this variant has b een reported in equal frequencies in cases and controls (Booij 2010, Clark 2010, Dreyer 2008, McGee 2010).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000755431	SCV000605548	benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000041881	SCV000704138	benign	not specified	2017-01-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000755431	SCV001097411	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000986532	SCV001135549	benign	Usher syndrome type 2A	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000755431	SCV001941371	benign	not provided	2018-12-20	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25412400, 18273898)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041881	SCV002500243	benign	not specified	2022-03-08	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.6240G>T (p.Lys2080Asn) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0056 in 251140 control chromosomes, predominantly at a frequency of 0.01 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. This frequency is almost close to that estimated for a pathogenic variant in USH2A causing Usher Syndrome (0.0056 vs 0.011), supporting a benign outcome. To our knowledge, no penetrant association of c.6240G>T in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and a predominant consensus as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000755431	SCV004125613	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	USH2A: BP4, BS2
Genome-Nilou Lab	RCV003450868	SCV004181686	likely benign	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000986532	SCV004181687	likely benign	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000755431	SCV005280582	benign	not provided		criteria provided, single submitter	not provided
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504996	SCV000598819	uncertain significance	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Natera, Inc.	RCV000986532	SCV001462250	benign	Usher syndrome type 2A	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041881	SCV001925587	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000041881	SCV001951978	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000755431	SCV001974903	likely benign	not provided		no assertion criteria provided	clinical testing