Submissions for variant NM_206933.4(USH2A):c.675_678del (p.Phe225fs)

dbSNP: rs2102708663

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001388346	SCV001589281	pathogenic	not provided	2022-07-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1074900). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe225Leufs*17) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381).
Myriad Genetics, Inc.	RCV002307743	SCV002604301	likely pathogenic	Usher syndrome type 2A	2022-02-25	criteria provided, single submitter	clinical testing	NM_206933.2(USH2A):c.675_678delCTTT(F225Lfs*17) is expected to be pathogenic in the context of USH2A-related disorders. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in USH2A, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.
Lifecell International Pvt. Ltd	RCV002307743	SCV003853260	pathogenic	Usher syndrome type 2A		criteria provided, single submitter	clinical testing	A Heterozygous Frameshift variant c.675_678delCTTT in Exon 4 of the USH2A gene that results in the premature termination of the protein (p.Phe225fs*17) was identified. The observed variant has a minimum allele frequency of 0.00% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. The variant was found in ClinVar (Variant ID :1074900) with a classification of Pathogenic/Likely Pathogenic and a review status of (2 star) criteria provided, multiple submitters, no conflicts.. Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.
Genome-Nilou Lab	RCV002307743	SCV004182960	likely pathogenic	Usher syndrome type 2A	2023-11-04	criteria provided, single submitter	clinical testing