Submissions for variant NM_206933.4(USH2A):c.9915G>C (p.Glu3305Asp)

gnomAD frequency: 0.00031  dbSNP: rs145278250

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041961	SCV000065657	benign	not specified	2017-09-04	criteria provided, single submitter	clinical testing	p.Glu3305Asp in exon 50 of USH2A: This variant is not expected to have clinical significance because it is has been identified in 1.57% (297/18854) of East Asia n chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadins titute.org; dbSNP rs145278250).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000910459	SCV001055326	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000910459	SCV001810742	likely benign	not provided	2021-02-01	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23591405, 24938718)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041961	SCV002500137	benign	not specified	2022-03-05	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.9915G>C (p.Glu3305Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0011 in 251264 control chromosomes, predominantly at a frequency of 0.015 within the East Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in USH2A causing Usher Syndrome phenotype (0.011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. Although reported in the literature, to our knowledge, no penetrant association of c.9915G>C in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV002477136	SCV002796465	likely benign	Usher syndrome type 2A; Retinitis pigmentosa 39	2022-03-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000910459	SCV003800046	likely benign	not provided	2022-02-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000910459	SCV004125603	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	USH2A: BP4, BS1
Genome-Nilou Lab	RCV003450917	SCV004182635	likely benign	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001276953	SCV004182636	likely benign	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003888415	SCV004707899	benign	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Natera, Inc.	RCV001276953	SCV001463646	benign	Usher syndrome type 2A	2020-01-17	no assertion criteria provided	clinical testing