Submissions for variant NM_206933.4(USH2A):c.5624A>G (p.Asn1875Ser)

gnomAD frequency: 0.00107  dbSNP: rs141609561

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155327	SCV000205013	likely benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	Asn1875Ser in Exon 28 of USH2A: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (12/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs141609561).
Invitae	RCV000891558	SCV001035380	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Mendelics	RCV000986533	SCV001135550	benign	Usher syndrome type 2A	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000891558	SCV001764525	uncertain significance	not provided	2021-04-19	criteria provided, single submitter	clinical testing	Reported in a patient with retinitis pigmentosa in published literature (Wang et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25097241)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000155327	SCV002512000	uncertain significance	not specified	2022-04-06	criteria provided, single submitter	clinical testing	Variant summary: USH2A c.5624A>G (p.Asn1875Ser) results in a conservative amino acid change located in the Fibronectin type III domain of 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 0.00028 in 250676 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in USH2A causing Usher Syndrome (0.00028 vs 0.011), allowing no conclusion about variant significance. c.5624A>G has been reported in the literature in an individual affected with retinitis pigmentosa (Wang_2014). This report does not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two submitters have classified as likely benign/benign while two classified as VUS. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003937460	SCV004749254	likely benign	USH2A-related condition	2023-07-18	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc.	RCV000986533	SCV001455632	uncertain significance	Usher syndrome type 2A	2020-01-24	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000891558	SCV001959061	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000891558	SCV001966812	uncertain significance	not provided		no assertion criteria provided	clinical testing