Submissions for variant NM_206933.4(USH2A):c.13709G>A (p.Arg4570His)

gnomAD frequency: 0.00158  dbSNP: rs730254

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041745	SCV000065441	benign	not specified	2011-11-03	criteria provided, single submitter	clinical testing	Arg4570His in exon 63 of USH2A: This variant has been identified in a proband wi th Usher syndrome type 2 and in a proband with nonsyndromic retinitis pigmentosa (McGee 2010). However, in both cases the variant was in heterozygous form witho ut a variant on the second allele and this variant was classified as benign (McG ee 2010). This is consistent with our computational analyses (PolyPhen, SIFT, Al ignGVGD) which do not suggest a high likelihood of impact to the protein. In add ition, this variant has also been reported in dbSNP with a frequency of 0.6% (43 /6927) control chromosomes (rs730254). In summary, this evidence suggests the va riant is benign.
Eurofins Ntd Llc (ga)	RCV000041745	SCV000332495	likely benign	not specified	2015-10-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000585560	SCV000692662	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	USH2A: BP4
GeneDx	RCV000041745	SCV000730479	likely benign	not specified	2018-02-07	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000585560	SCV001037460	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000041745	SCV001160361	likely benign	not specified	2019-02-15	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376370	SCV001573487	uncertain significance	Retinitis pigmentosa 39	2021-04-08	criteria provided, single submitter	research	The USH2A c.13709G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: BP4. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Genome-Nilou Lab	RCV001272941	SCV001737211	likely benign	Usher syndrome type 2A	2021-05-18	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003887893	SCV004707236	likely benign	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Natera, Inc.	RCV001272941	SCV001455392	benign	Usher syndrome type 2A	2020-01-13	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000585560	SCV001920692	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000585560	SCV001972810	likely benign	not provided		no assertion criteria provided	clinical testing