1-215675172-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_206933.4(USH2A):c.12739G>A(p.Gly4247Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,808 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). Synonymous variant affecting the same amino acid position (i.e. G4247G) has been classified as Likely benign.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.12739G>A | p.Gly4247Arg | missense_variant | 63/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.12739G>A | p.Gly4247Arg | missense_variant | 63/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.12739G>A | p.Gly4247Arg | missense_variant | 63/73 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250788Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135528
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461808Hom.: 0 Cov.: 37 AF XY: 0.00000275 AC XY: 2AN XY: 727200
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Usher syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | research | SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation | Dec 31, 2022 | - - |
Rare genetic deafness Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 15, 2011 | The Gly4247Arg variant in USH2A has not been reported in the literature nor prev iously identified by our laboratory. This residue is highly conserved across spe cies and computational analyses (PolyPhen2, SIFT, AlignGVGD) suggest that the Gl y4247Arg variant may impact the protein. In addition, this variant was identifed in trans with another pathogenic variant in USH2A. In summary, this data sugges ts that this variant is likely to be pathogenic. - |
Usher syndrome type 2A Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at