rs1553250627
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_206933.4(USH2A):c.1397G>T(p.Gly466Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,338 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. G466G) 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_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.1397G>T | p.Gly466Val | missense_variant | 8/72 | ENST00000307340.8 | |
USH2A | NM_007123.6 | c.1397G>T | p.Gly466Val | missense_variant | 8/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.1397G>T | p.Gly466Val | missense_variant | 8/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000366942.3 | c.1397G>T | p.Gly466Val | missense_variant | 8/21 | 1 | |||
USH2A | ENST00000674083.1 | c.1397G>T | p.Gly466Val | missense_variant | 8/73 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151926Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461412Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727006
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151926Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74176
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 466 of the USH2A protein (p.Gly466Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 24938718, 31960602; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 554616). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt USH2A protein function. For these reasons, this variant has been classified as Pathogenic. - |
Retinitis pigmentosa 39 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 16, 2023 | - - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Oct 27, 2017 | - - |
Usher syndrome type 2A Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 27, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at