rs746098518
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000307340.8(USH2A):c.15322C>T(p.Arg5108Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R5108R) has been classified as Likely benign.
Frequency
Consequence
ENST00000307340.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.15322C>T | p.Arg5108Trp | missense_variant | 71/72 | ENST00000307340.8 | NP_996816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.15322C>T | p.Arg5108Trp | missense_variant | 71/72 | 1 | NM_206933.4 | ENSP00000305941 | P1 | |
USH2A | ENST00000674083.1 | c.15394C>T | p.Arg5132Trp | missense_variant | 72/73 | ENSP00000501296 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251096Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135752
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461020Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726832
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 11, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Arg5108Trp va riant in USH2A has not been previously reported in individuals with hearing loss , but has been identified in 1/16490 of South Asian chromosomes and in 1/11562 o f Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs746098518). Arginine (Arg) at position 5108 is not conse rved in mammals or evolutionarily distant species and 2 mammals (Tibetan antelop e and armadillo) carry tryptophan (Trp) at this position, raising the possibilit y that this change may be tolerated. In summary, while the clinical significance of the p.Arg5108Trp variant is uncertain, these data suggest that it is more li kely to be benign. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 15, 2024 | Variant summary: USH2A c.15322C>T (p.Arg5108Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251096 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.15322C>T has been reported in the literature in individuals affected with Retinal degeneration (Zampaglione_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 32037395). ClinVar contains an entry for this variant (Variation ID: 229623). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Usher syndrome type 2A Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 28, 2016 | - - |
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