rs112120466
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_StrongBP6BS2_Supporting
The NM_206933.4(USH2A):āc.12557T>Cā(p.Ile4186Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,614,108 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I4186I) has been classified as Likely benign.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.12557T>C | p.Ile4186Thr | missense_variant | 63/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.12557T>C | p.Ile4186Thr | missense_variant | 63/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.12557T>C | p.Ile4186Thr | missense_variant | 63/73 |
Frequencies
GnomAD3 genomes AF: 0.00145 AC: 220AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000480 AC: 120AN: 249872Hom.: 0 AF XY: 0.000348 AC XY: 47AN XY: 135152
GnomAD4 exome AF: 0.000186 AC: 272AN: 1461834Hom.: 2 Cov.: 37 AF XY: 0.000166 AC XY: 121AN XY: 727212
GnomAD4 genome AF: 0.00151 AC: 230AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.00153 AC XY: 114AN XY: 74450
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 11, 2020 | - - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Aug 28, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Ile4186Thr in Exon 63 of USH2A: This variant is not expected to have clinical si gnificance because it has been identified in 0.6% (22/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs112120466). - |
Usher syndrome type 2A Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 22, 2019 | - - |
USH2A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 05, 2023 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at