rs111033508
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6
The NM_206933.4(USH2A):c.7060C>T(p.Arg2354Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,613,902 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2354H) has been classified as Uncertain significance.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.7060C>T | p.Arg2354Cys | missense_variant | 37/72 | ENST00000307340.8 | NP_996816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.7060C>T | p.Arg2354Cys | missense_variant | 37/72 | 1 | NM_206933.4 | ENSP00000305941.3 | ||
USH2A | ENST00000674083.1 | c.7060C>T | p.Arg2354Cys | missense_variant | 37/73 | ENSP00000501296.1 |
Frequencies
GnomAD3 genomes AF: 0.00106 AC: 162AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000330 AC: 83AN: 251262Hom.: 0 AF XY: 0.000272 AC XY: 37AN XY: 135784
GnomAD4 exome AF: 0.000239 AC: 349AN: 1461620Hom.: 1 Cov.: 31 AF XY: 0.000210 AC XY: 153AN XY: 727112
GnomAD4 genome AF: 0.00108 AC: 164AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000953 AC XY: 71AN XY: 74464
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 14, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 25, 2017 | p.Arg2354Cys in exon 37 of USH2A: This variant is not expected to have clinical significance because it has been identified in 0.4% (45/10402) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs111033508). - |
Usher syndrome type 2A Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 07, 2019 | - - |
USH2A-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 03, 2024 | The USH2A c.7060C>T variant is predicted to result in the amino acid substitution p.Arg2354Cys. This variant was reported along with a second variant in USH2A in an individual with hearing loss (Table S3 in Sloan-Heggen et al 2016. PubMed ID: 26969326). This variant is reported in 0.38% of alleles in individuals of African descent in gnomAD, which is likely too common to be a primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at