rs878853412
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_206933.4(USH2A):āc.6118T>Gā(p.Cys2040Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C2040R) has been classified as Uncertain significance.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.6118T>G | p.Cys2040Gly | missense_variant | 31/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.6118T>G | p.Cys2040Gly | missense_variant | 31/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.6118T>G | p.Cys2040Gly | missense_variant | 31/73 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727208
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Retinal dystrophy Pathogenic:1Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals | - | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Mar 08, 2019 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2022 | This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 2040 of the USH2A protein (p.Cys2040Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 27208204, 28041643). ClinVar contains an entry for this variant (Variation ID: 236543). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 16, 2016 | - - |
Retinitis pigmentosa 39 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 18, 2023 | - - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Sep 24, 2017 | - - |
Usher syndrome type 2A Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 27, 2021 | - - |
Retinitis pigmentosa Uncertain:1
Uncertain significance, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at