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

gnomAD frequency: 0.00063  dbSNP: rs111033333

Total submissions: 10

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, Mass General Brigham 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)
Eurofins Ntd Llc (ga)	RCV000041847	SCV000227976	benign	not specified	2014-11-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000087011	SCV000493417	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	USH2A: BS2
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	2024-01-30	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