rs869312182
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PP4PM2PM3_Strong
This summary comes from the ClinGen Evidence Repository: The c.6446C>A (p.Pro2149Gln) variant in USH2A was absent from gnomAD (PM2). It has been detected in one patient with Usher syndrome and one patient with isolated Retinitis pigmentosa, both of whom carried another suspected pathogenic variant in trans (PM3_Strong; PP4; PMIDs: 26872967, 29074561, 28041643; ClinVar ID: 2356). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied as specified by the Hearing Loss Expert Panel: PM2, PM3_Strong, PP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA354063/MONDO:0019501/005
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.6446C>A | p.Pro2149Gln | missense_variant | 33/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.6446C>A | p.Pro2149Gln | missense_variant | 33/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.6446C>A | p.Pro2149Gln | missense_variant | 33/73 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461376Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726978
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Usher syndrome Pathogenic:1
Likely pathogenic, reviewed by expert panel | curation | ClinGen Hearing Loss Variant Curation Expert Panel | May 26, 2020 | The c.6446C>A (p.Pro2149Gln) variant in USH2A was absent from gnomAD (PM2). It has been detected in one patient with Usher syndrome and one patient with isolated Retinitis pigmentosa, both of whom carried another suspected pathogenic variant in trans (PM3_Strong; PP4; PMIDs: 26872967, 29074561, 28041643; ClinVar ID: 2356). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied as specified by the Hearing Loss Expert Panel: PM2, PM3_Strong, PP4. - |
Usher syndrome type 2A Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals | Aug 28, 2015 | - - |
Retinitis pigmentosa Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Retinal dystrophy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at