1-215674957-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.12954C>A(p.Tyr4318*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,874 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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y4318Y) 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
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461874Hom.: 0 Cov.: 37 AF XY: 0.00000688 AC XY: 5AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Retinitis pigmentosa 39 Pathogenic:4
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Usher syndrome Pathogenic:1
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Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Pathogenic:1
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not provided Pathogenic:1
This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 18273898, 20507924, 28041643). This sequence change creates a premature translational stop signal (p.Tyr4318*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 438009). For these reasons, this variant has been classified as Pathogenic. -
Retinal dystrophy Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at