rs1338169194
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_206933.4(USH2A):βc.895delβ(p.Gln299AsnfsTer37) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. Q299Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_206933.4 frameshift
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.895del | p.Gln299AsnfsTer37 | frameshift_variant | 6/72 | ENST00000307340.8 | |
USH2A | NM_007123.6 | c.895del | p.Gln299AsnfsTer37 | frameshift_variant | 6/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.895del | p.Gln299AsnfsTer37 | frameshift_variant | 6/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000366942.3 | c.895del | p.Gln299AsnfsTer37 | frameshift_variant | 6/21 | 1 | |||
USH2A | ENST00000674083.1 | c.895del | p.Gln299AsnfsTer37 | frameshift_variant | 6/73 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152048Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250300Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135278
GnomAD4 exome Cov.: 31
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74250
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 438031). This premature translational stop signal has been observed in individual(s) with USH2A-related conditions (PMID: 28041643, 28894305). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln299Asnfs*37) 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
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 20, 2023 | - - |
Usher syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at