rs1553248234
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_206933.4(USH2A):βc.15322delCβ(p.Arg5108fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. R5108R) has been classified as Likely benign.
Frequency
Consequence
NM_206933.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.15322delC | p.Arg5108fs | frameshift_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.15322delC | p.Arg5108fs | frameshift_variant | 71/72 | 1 | NM_206933.4 | ENSP00000305941.3 | ||
USH2A | ENST00000674083.1 | c.15394delC | p.Arg5132fs | frameshift_variant | 72/73 | ENSP00000501296.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461082Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726862
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Dec 05, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 05, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 555433). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 25575603). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg5108Glyfs*6) 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). - |
Retinitis pigmentosa 39 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Usher syndrome type 2A Pathogenic:1
Likely 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