rs1553261469
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The ENST00000307340.8(USH2A):āc.10415A>Gā(p.Tyr3472Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,432 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y3472H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000307340.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.10415A>G | p.Tyr3472Cys | missense_variant | 53/72 | ENST00000307340.8 | NP_996816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.10415A>G | p.Tyr3472Cys | missense_variant | 53/72 | 1 | NM_206933.4 | ENSP00000305941 | P1 | |
USH2A | ENST00000674083.1 | c.10415A>G | p.Tyr3472Cys | missense_variant | 53/73 | ENSP00000501296 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461432Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726998
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Usher syndrome type 2A Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 26, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 27, 2017 | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Tyr3472Cy s variant in USH2A has been reported by our laboratory in one individual with he aring loss, who has another variant of uncertain significance on the same copy a nd a pathogenic variant on the other copy of the USH2A gene. The p.Tyr3472Cys va riant has not been identified in large population studies. Computational predict ion tools and conservation analyses suggest that this variant may impact the pro tein, and splice prediction tools suggest the possible creation of a 5' cryptic splice site; however, this information is not predictive enough to determine pat hogenicity. In summary, while there is some suspicion of a pathogenic role, the clinical significance of the p.Tyr3472Cys variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 08, 2020 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, 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