Submissions for variant NM_206933.4(USH2A):c.8790T>G (p.Asn2930Lys)

gnomAD frequency: 0.00006  dbSNP: rs754774098

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001073861	SCV001239425	uncertain significance	Retinal dystrophy	2018-07-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811643	SCV001471629	uncertain significance	not provided	2019-08-18	criteria provided, single submitter	clinical testing	The USH2A c.8790T>G; p.Asn2930Lys variant (rs754774098) is reported in the literature in several individuals affected with retinitis pigmentosa, although it was not demonstrated to be disease-causing in these individuals (McGee 2010). This variant is found in the general population with an overall allele frequency of 0.004% (10/282720 alleles) in the Genome Aggregation Database. The asparagine at codon 2930 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Asn2930Lys variant is uncertain at this time. References: McGee TL et al. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. J Med Genet. 2010 Jul;47(7):499-506.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001811643	SCV003253021	uncertain significance	not provided	2022-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 2930 of the USH2A protein (p.Asn2930Lys). This variant is present in population databases (rs754774098, gnomAD 0.02%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 20507924). ClinVar contains an entry for this variant (Variation ID: 866103). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt USH2A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV003455334	SCV004182769	uncertain significance	Retinitis pigmentosa 39	2023-11-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001833685	SCV004182770	uncertain significance	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001833685	SCV002090804	uncertain significance	Usher syndrome type 2A	2020-08-08	no assertion criteria provided	clinical testing