1-215900194-G-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_206933.4(USH2A):c.7475C>A(p.Ser2492Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,461,286 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S2492S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_206933.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.7475C>A | p.Ser2492Ter | stop_gained | 40/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.7475C>A | p.Ser2492Ter | stop_gained | 40/72 | 1 | NM_206933.4 | P1 | |
ENST00000414995.1 | n.61-531G>T | intron_variant, non_coding_transcript_variant | 3 | ||||||
USH2A | ENST00000674083.1 | c.7475C>A | p.Ser2492Ter | stop_gained | 40/73 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461286Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726920
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Usher syndrome type 2A Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | literature only | Molecular Genetics Laboratory; Baylor College of Medicine | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2015 | The S2492X nonsense variant in the USH2A gene is predicted to cause loss of normal protein functioneither through protein truncation or nonsense-mediated mRNA decay. S2492X was notobserved in approximately 6,500 individuals of European and African American ancestry in the NHLBIExome Sequencing Project, indicating it is not a common benign variant in these populations. Although thisvariant has not been reported previously to our knowledge, we consider it to be pathogenic. - |
Retinitis pigmentosa 39 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at